2022 U.S. Open Cup#Third Round

{{main|2022 U.S. Open Cup qualification}}

Pro teams that are majority-owned or controlled by higher division professional clubs are barred from entering the competition. For this edition of the tournament, there are 21 such teams: Atlanta United 2 (USLC), LA Galaxy II (USLC), Loudoun United FC (USLC), New York Red Bulls II (USLC), and 17 out of 19 MLS Next Pro teams. The two MLS Next Pro teams entering are Rochester New York FC (independent club) and St. Louis City 2 (the club's senior team does not debut until the 2023 season).

• Bold denotes team is still active in the tournament.
• {{anchor|Money}} $: Winner of $25,000 bonus for advancing the furthest in the competition from their respective divisions.
• {{anchor|Runner-up}} $$: Winner of $100,000 for being the runner-up in the competition.
• {{anchor|Champion}} $$$: Winner of $300,000 for winning the competition.

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{{reflist|group=lower-roman}}

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{{Location map+ |USA |width=1300 |float=center |caption=Locations of teams in the tournament proper.

{{hlist

| 8px MLS

| 8px USLC

| 8px Division 3 (MLS Next Pro/NISA/USL1)

| 8px Open Division (NPSL/USL2)

| 8px Local Qualifiers & National Amateur Cup Champion

| 8px Multiple Teams

}}

Metro areas with multiple teams:

Atlanta: Atlanta United FC (MLS), Georgia Revolution FC (NPSL)

Boston: New England Revolution (MLS), Brockton FC United (Local)

Charlotte: Charlotte FC (MLS), Charlotte Independence (USL1)

Chattanooga: Chattanooga FC (NISA), Chattanooga Red Wolves SC (USL1)

Chicago: Chicago Fire FC (MLS), Chicago FC United (USL2)

Dallas: FC Dallas (MLS), Denton Diablos FC (NPSL), D'Feeters Kicks Soccer Club (Local)

Denver: Colorado Rapids (MLS), Azteca FC (Local)

Detroit: Detroit City FC (USLC), Michigan Stars FC (NISA)

Hartford: Hartford Athletic (USLC), Hartford City FC (NPSL)

Las Vegas: Las Vegas Lights FC (USLC), Las Vegas Legends (NPSL)

Los Angeles: Los Angeles FC (MLS), LA Galaxy (MLS), Orange County SC (USLC), California United Strikers FC (NISA), Los Angeles Force (NISA), San Fernando Valley FC (Local)

Miami: Inter Miami CF (MLS), Miami FC (USLC), Miami United FC (NPSL)

Minneapolis/St. Paul: Minnesota United FC (MLS), Minneapolis City SC (NPSL)

New York City: New York City FC (MLS), New York Red Bulls (MLS), FC Motown (NPSL), Lansdowne Yonkers FC (Local), Oyster Bay United FC (Local)

Orlando: Orlando City SC (MLS), Orlando FC Wolves (Local)

Philadelphia: Philadelphia Union (MLS), West Chester United SC (USL2)

Phoenix: Phoenix Rising FC (USLC), Valley United FC (NISA)

Rochester: Rochester New York FC (MLS Next Pro), Flower City Union (NISA)

San Diego: San Diego Loyal SC (USLC), Albion San Diego (NISA)

San Francisco Bay Area: San Jose Earthquakes (MLS), Oakland Roots SC (USLC), Bay Cities FC (NISA), Contra Costa FC (Local)

Tulsa: FC Tulsa (USLC), Tulsa Athletic (NPSL)

Washington, D.C.: D.C. United (MLS), Northern Virginia FC (Local)

|places=

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{{Location map~ |USA |lat=39.11103328098898 |long=-84.52285872056366 |label=FC Cincinnati |label_size=80 |position=top |mark=Red pog.svg}}

{{Location map~ |USA |lat=39.968451656675654 |long=-83.01709494651429 |label=Columbus Crew |label_size=80 |position=right |mark=Red pog.svg}}

{{Location map~ |USA |lat=29.752255671778688 |long=-95.35222014719191 |label=Houston Dynamo FC |label_size=80 |position=right |mark=Red pog.svg}}

{{Location map~ |USA |lat=36.16646779431836 |long=-86.77128726417052 |label=Nashville SC |label_size=80 |position=right |mark=Red pog.svg}}

{{Location map~ |USA |lat=45.51517179226837 |long=-122.67834753903254 |label=Portland Timbers |label_size=80 |position=top |mark=Red pog.svg}}

{{Location map~ |USA |lat=40.582929184372404 |long=-111.8933594914704 |label=Real Salt Lake |label_size=80 |position=left |mark=Red pog.svg}}

{{Location map~ |USA |lat=47.59513326556388 |long=-122.33164865965206 |label=Seattle Sounders FC |label_size=80 |position=left |mark=Red pog.svg}}

{{Location map~ |USA |lat=39.12163118064744 |long=-94.8231994975958 |label=Sporting Kansas City |label_size=80 |position=left |mark=Red pog.svg}}

{{Location map~ |USA |lat=33.51860982216501 |long=-86.81046673158751 |label=Birmingham Legion FC |label_size=80 |position=left |mark=Orange pog.svg}}

{{Location map~ |USA |lat=32.77649521763172 |long=-79.9309881312091 |label=Charleston Battery |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=38.83390079067579 |long=-104.82150063775298 |label=Colorado Springs Switchbacks FC |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=31.761954479179543 |long=-106.48492429902919 |label=El Paso Locomotive FC |label_size=80 |position=top |mark=Orange pog.svg}}

{{Location map~ |USA |lat=39.7684897971886 |long=-86.15803260219954 |label=Indy Eleven |label_size=80 |position=left |mark=Orange pog.svg}}

{{Location map~ |USA |lat=38.252709073571815 |long=-85.75850187080235 |label=Louisville City FC |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=35.14951896545076 |long=-90.04905223697526 |label=Memphis 901 FC |label_size=80 |position=left |mark=Orange pog.svg}}

{{Location map~ |USA |lat=36.61490418002709 |long=-121.82204912721032 |label=Monterey Bay FC |label_size=80 |position=left |mark=Orange pog.svg}}

{{Location map~ |USA |lat=35.08418344509937 |long=-106.65086953523182 |label=New Mexico United |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=40.44066553092845 |long=-79.99595433437983 |label=Pittsburgh Riverhounds SC |label_size=80 |position=top |mark=Orange pog.svg}}

{{Location map~ |USA |lat=26.301726364795066 |long=-98.16334476174318 |label=Rio Grande Valley FC |label_size=80 |position=top |mark=Orange pog.svg}}

{{Location map~ |USA |lat=38.58173860292029 |long=-121.4945425441788 |label=Sacramento Republic FC |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=29.424126971749406 |long=-98.49371772852207 |label=San Antonio FC |label_size=80 |position=right |mark=Orange pog.svg}}

{{Location map~ |USA |lat=27.76760384836234 |long=-82.64016609082519 |label=Tampa Bay Rowdies |label_size=80 |position=left |mark=Orange pog.svg}}

{{Location map~ |USA |lat=38.62692745995879 |long=-90.19915023580369 |label=St. Louis City 2 |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=39.18501420930216 |long=-77.3106495526165 |label=Maryland Bobcats FC |label_size=80 |position=top |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=43.04816140032028 |long=-76.14745003388273 |label=AC Syracuse Pulse |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=36.73782216056503 |long=-119.7871543150927 |label=Central Valley Fuego FC |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=43.07305651659342 |long=-89.40122671893994 |label=Forward Madison FC |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=34.85263694973682 |long=-82.39409386584747 |label=Greenville Triumph SC |label_size=80 |position=bottom |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=35.79143485820475 |long=-78.78113885194223 |label=North Carolina FC |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=40.477479786508205 |long=-104.90135727746456 |label=Northern Colorado Hailstorm FC |label_size=80 |position=top |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=37.54069231180277 |long=-77.4360245445324 |label=Richmond Kickers |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=32.44881401911466 |long=-81.78325284439606 |label=South Georgia Tormenta FC |label_size=80 |position=bottom |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=32.22261185497297 |long=-110.97468867324034 |label=FC Tucson |label_size=80 |position=right |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=41.2565273110203 |long=-95.93449814923649 |label=Union Omaha |label_size=80 |position=left |mark=Yellow pog.svg}}

{{Location map~ |USA |lat=41.499263207713454 |long=-81.69458163384819 |label=Cleveland SC |label_size=80 |position=left |mark=Green pog.svg}}

{{Location map~ |USA |lat=31.327094208319302 |long=-89.29039244169711 |label=Southern States SC |label_size=80 |position=top |mark=Green pog.svg}}

{{Location map~ |USA |lat=41.58681948015526 |long=-93.62491357165688 |label=Des Moines Menace |label_size=80 |position=top |mark=Green pog.svg}}

{{Location map~ |USA |lat=36.21271615454268 |long=-79.71326524106982 |label=NC Fusion |label_size=80 |position=left |mark=Green pog.svg}}

{{Location map~ |USA |lat=39.27763593037902 |long=-74.57471625452628 |label=Ocean City Nor'easters |label_size=80 |position=right |mark=Green pog.svg}}

{{Location map~ |USA |lat=40.646066141574664 |long=-111.49798428929655 |label=Park City Red Wolves SC |label_size=80 |position=right |mark=Green pog.svg}}

{{Location map~ |USA |lat=44.944099 |long=-123.040283 |label=Portland Timbers U23 |label_size=80 |position=right |mark=Green pog.svg}}

{{Location map~ |USA |lat=34.000759578073264 |long=-81.0349980982143 |label=South Carolina United |label_size=80 |position=right |mark=Green pog.svg}}

{{Location map~ |USA |lat=29.007573324329734 |long=-82.02047843661448 |label=The Villages SC |label_size=80 |position=left |mark=Green pog.svg}}

{{Location map~ |USA |lat=42.16010957326859 |long=-72.47594487801534 |label=Western Mass Pioneers |label_size=80 |position=top |mark=Green pog.svg}}

{{Location map~ |USA |lat=26.7152685529129 |long=-80.0534491801158 |label=City Soccer FC |label_size=80 |position=right |mark=Blue pog.svg}}

{{Location map~ |USA |lat=33.11918834957731 |long=-117.08640778560493 |label=Escondido FC |label_size=80 |position=right |mark=Blue pog.svg}}

{{Location map~ |USA |lat=37.41375048830848 |long=-79.14221557162479 |label=Lynchburg FC |label_size=80 |position=left |mark=Blue pog.svg}}

{{Location map~ |USA |lat=33.74899537073518 |long=-84.3879717810452 |label=Atlanta |label_size=80 |position=right |mark=Purple pog.svg}}

{{Location map~ |USA |lat=42.36000864641099 |long=-71.05897195039502 |label=Boston |label_size=80 |position=right |mark=Purple pog.svg}}

{{Location map~ |USA |lat=35.22721552837581 |long=-80.84309227188619 |label=Charlotte |label_size=80 |position=top |mark=Purple pog.svg}}

{{Location map~ |USA |lat=35.045719432756805 |long=-85.31043593018825 |label=Chattanooga |label_size=80 |position=left |mark=Purple pog.svg}}

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{{Location map~ |USA |lat=32.776641272898054 |long=-96.79687666526628 |label=Dallas |label_size=80 |position=bottom |mark=Purple pog.svg}}

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{{Location map~ |USA |lat=39.73933852440657 |long=-104.99016710747496 |label=Denver |label_size=80 |position=left |mark=Purple pog.svg}}

{{Location map~ |USA |lat=42.331506643194736 |long=-83.04569005672376 |label=Detroit |label_size=80 |position=left |mark=Purple pog.svg}}

{{Location map~ |USA |lat=41.76584042503873 |long=-72.67333170291519 |label=Hartford |label_size=80 |position=right |mark=Purple pog.svg}}

{{Location map~ |USA |lat=36.16922858479163 |long=-115.14065221352614 |label=Las Vegas |label_size=80 |position=top |mark=Purple pog.svg}}

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{{Location map~ |USA |lat=25.761707708487393 |long=-80.1919419163021 |label=Miami |label_size=80 |position=right |mark=Purple pog.svg}}

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{{Location map~ |USA |lat=36.15399014678964 |long=-95.99281508409018 |label=Tulsa |label_size=80 |position=right |mark=Purple pog.svg}}

}}

A total of 35 states and the District of Columbia are represented by clubs in the U.S. Open Cup this year.

States without a team in the Open Cup: Alaska, Arkansas, Delaware, Hawaii, Idaho, Louisiana, Maine, Montana, New Hampshire, North Dakota, Rhode Island, South Dakota, Vermont, West Virginia, and Wyoming.

31 teams played in their first Open Cup tournament in 2022.

• MLS: Austin FC, Charlotte FC, Inter Miami CF
• USLC: Monterey Bay FC, Oakland Roots SC, Rio Grande Valley FC Toros, San Diego Loyal SC
• MLS Next Pro: St. Louis City 2
• NISA: Albion San Diego, AC Syracuse Pulse, Bay Cities FC, California United Strikers FC, Flower City Union, Los Angeles Force, Maryland Bobcats FC, Michigan Stars FC, Valley United FC
• USL1: Central Valley Fuego FC, Northern Colorado Hailstorm FC, Union Omaha
• NPSL: Cleveland SC, Denton Diablos FC, Southern States Soccer Club, Las Vegas Legends
• USL2: Minneapolis City SC, Park City Red Wolves SC
• UPSL: Escondido FC, Lynchburg FC, Oyster Bay United FC, San Fernando Valley FC
• Other Open Division: Brockton FC United, D'Feeters Kicks SC

Due to their league's scheduling, Northern Colorado Hailstorm FC's 1-0 victory in the Second Round was the first time in the U.S. Open Cup's modern era that a club recorded their first-ever competitive match, goal, and victory in the Open Cup.

• No team who was playing their first Open Cup match was paired with another team also playing their first Open Cup match. An exception was made if there were no other teams that were geographically close in order to prevent excess travel.
• Random pairings were done in cases where three or more teams were from the same general area.
• In cases where a geographical fit didn't exist, a random selection occurred.
• Pairings between clubs and their parent clubs, clubs with shared ownership, or other clubs using the same technical resources was avoided in geographic selections and random pairings until the final. For 2022, these pairings included: Los Angeles FC (MLS) and Las Vegas Lights (USLC), Portland Timbers (MLS) and Portland Timbers U23 (USL2), Chattanooga Red Wolves SC (USL1) and Park City Red Wolves SC (USL2).

• Single-game-knockout format with two 45-minute halves and stoppage time.
• Tied matches are sent to two 15-minute extra time halves with stoppage time.
• Matches tied after extra time will be settled with a penalty shootout.
• Home teams are determined by a random selection among teams that apply to host. Teams that meet minimum tournament standards will be given priority over others in their pairing.
• Five substitutions during regulation time over three substitution windows and halftime.
• One extra substitution added during extra time. This substitution can be made at the end of regulation, over an additional substitution window, or at extra time halftime.
• Up to two extra substitutions over two extra substitution windows will be available in the case of a concussion. If a team uses this concussion substitution, the opposing team gains an additional substitution and substitution window.

In the First round, teams (local, National Amateur Cup, NPSL, & USL2) were paired in a geographical manner, pitting teams closer together against each other. Once the First round pairings were made those pairings were matched with a Division II (USLC) or a Division III (MLS Next Pro, NISA, or USL1) team in a geographical manner for the Second round. Division II & III teams that remained unmatched were matched together, again geographically, avoiding any same-division matching (e.g., no II vs II or III vs III).

The complete draw for the First round, including match dates and times, was announced on February 2, 2022.{{cite press release |date=February 2, 2022 |title=Thirty-Two Open Division Teams Learn First Round Opponent For 2022 Lamar Hunt U.S. Open Cup |url=https://www.ussoccer.com/stories/2022/02/thirty-two-open-division-teams-learn-first-round-opponent-for-2022-lamar-hunt-us-open-cup |publisher=United States Soccer Federation |access-date=February 3, 2022}} Draws for the Second round were announced on February 11; match dates and times were announced on February 28.{{cite press release |date=February 11, 2022 |title=U.S. Soccer Releases Second Round Pairings and Host Scenarios For 2022 Lamar Hunt U.S. Open Cup |url=https://www.ussoccer.com/stories/2022/02/us-soccer-releases-second-round-pairings-and-host-scenarios-for-2022-lamar-hunt-us-open-cup |publisher=United States Soccer Federation |access-date=February 11, 2022}}{{cite press release |date=February 28, 2022 |title=U.S. Soccer Releases Second Round Match Schedule For 2022 Lamar Hunt U.S. Open Cup |url=https://www.ussoccer.com/stories/2022/02/second-round-match-schedule-announced-for-2022-lamar-hunt-us-open-cup |publisher=United States Soccer Federation |access-date=February 28, 2022}}

{{2NTeam-NTeamBracket

| rounds = 2

| brackets = 31

| RD1-byes = y

| boldwinner = y

| seed-width = 50

| team-width = 205

| score-width = 30

| RD1 = First round
March 22–23

| RD2 = Second round
April 5–7

| RD1-seed01 = NPSL

| RD1-team01 = FC Motown

| RD1-score01 = 1

| RD1-seed02 = USL2

| RD1-team02 = West Chester United SC

| RD1-score02 = 0

| RD1-seed05 = NPSL

| RD1-team05 = Hartford City FC

| RD1-score05 = 0

| RD1-seed06 = LQ

| RD1-team06 = Oyster Bay United FC

| RD1-score06 = 3

| RD1-seed09 = USL2

| RD1-team09 = South Carolina United

| RD1-score09 = 0

| RD1-seed10 = USL2

| RD1-team10 = North Carolina Fusion U23

| RD1-score10 = 1

| RD1-seed13 = USL2

| RD1-team13 = The Villages SC

| RD1-score13 = 6

| RD1-seed14 = LQ

| RD1-team14 = Orlando FC Wolves

| RD1-score14 = 0

| RD1-seed17 = NPSL

| RD1-team17 = Denton Diablos FC

| RD1-score17 = 2

| RD1-seed18 = LQ

| RD1-team18 = D'Feeters Kicks Soccer Club

| RD1-score18 = 3

| RD1-seed21 = NPSL

| RD1-team21 = Southern States Soccer Club

| RD1-score21 = 3

| RD1-seed22 = NPSL

| RD1-team22 = Georgia Revolution FC

| RD1-score22 = 1

| RD1-seed25 = LQ

| RD1-team25 = San Fernando Valley FC

| RD1-score25 = 6

| RD1-seed26 = LQ

| RD1-team26 = Escondido FC

| RD1-score26 = 2

| RD1-seed29 = LQ

| RD1-team29 = Lynchburg FC

| RD1-score29 = 1

| RD1-seed30 = LQ

| RD1-team30 = Northern Virginia FC

| RD1-score30 = 3

| RD1-seed33 = USL2

| RD1-team33 = Ocean City Nor'easters

| RD1-score33 = 1 (3)

| RD1-seed34 = NAC

| RD1-team34 = Lansdowne Yonkers FC

| RD1-score34 = 1 (4)

| RD1-seed37 = NPSL

| RD1-team37 = Cleveland SC

| RD1-score37 = 2*

| RD1-seed38 = USL2

| RD1-team38 = Chicago FC United

| RD1-score38 = 1

| RD1-seed41 = NPSL

| RD1-team41 = Miami United FC

| RD1-score41 = 3

| RD1-seed42 = LQ

| RD1-team42 = City Soccer FC

| RD1-score42 = 1

| RD1-seed45 = USL2

| RD1-team45 = Western Mass Pioneers

| RD1-score45 = 2

| RD1-seed46 = LQ

| RD1-team46 = Brockton FC United

| RD1-score46 = 0

| RD1-seed49 = USL2

| RD1-team49 = Des Moines Menace

| RD1-score49 = 3

| RD1-seed50 = NPSL

| RD1-team50 = Minneapolis City SC

| RD1-score50 = 2

| RD1-seed53 = NPSL

| RD1-team53 = Tulsa Athletic

| RD1-score53 = 3

| RD1-seed54 = LQ

| RD1-team54 = Azteca FC

| RD1-score54 = 0

| RD1-seed57 = USL2

| RD1-team57 = Portland Timbers U23s

| RD1-score57 = 2

| RD1-seed58 = LQ

| RD1-team58 = Contra Costa FC

| RD1-score58 = 1

| RD1-seed61 = NPSL

| RD1-team61 = Las Vegas Legends

| RD1-score61 = 3

| RD1-seed62 = USL2

| RD1-team62 = Park City Red Wolves SC

| RD1-score62 = 2

| RD2-seed01 = NISA

| RD2-team01 = AC Syracuse Pulse

| RD2-score01 = 0

| RD2-seed02 = NPSL

| RD2-team02 = FC Motown

| RD2-score02 = 1*

| RD2-seed03 = NISA

| RD2-team03 = Albion San Diego

| RD2-score03 = 1

| RD2-seed04 = USLC

| RD2-team04 = San Diego Loyal SC

| RD2-score04 = 2

| RD2-seed05 = USLC

| RD2-team05 = Hartford Athletic

| RD2-score05 = 3

| RD2-seed06 = LQ

| RD2-team06 = Oyster Bay United FC

| RD2-score06 = 1

| RD2-seed07 = NISA

| RD2-team07 = Bay Cities FC

| RD2-score07 = 2

| RD2-seed08 = USLC

| RD2-team08 = Monterey Bay FC

| RD2-score08 = 1

| RD2-seed09 = USL1

| RD2-team09 = Charlotte Independence

| RD2-score09 = 2

| RD2-seed10 = USL2

| RD2-team10 = North Carolina Fusion U23

| RD2-score10 = 4

| RD2-seed11 = USLC

| RD2-team11 = Charleston Battery

| RD2-score11 = 0

| RD2-seed12 = USL1

| RD2-team12 = South Georgia Tormenta FC

| RD2-score12 = 1

| RD2-seed13 = USLC

| RD2-team13 = Tampa Bay Rowdies

| RD2-score13 = 6

| RD2-seed14 = USL2

| RD2-team14 = The Villages SC

| RD2-score14 = 0

| RD2-seed15 = NISA

| RD2-team15 = Chattanooga FC

| RD2-score15 = 3

| RD2-seed16 = USLC

| RD2-team16 = Memphis 901 FC

| RD2-score16 = 1

| RD2-seed17 = USLC

| RD2-team17 = San Antonio FC

| RD2-score17 = 3

| RD2-seed18 = LQ

| RD2-team18 = D'Feeters Kicks Soccer Club

| RD2-score18 = 1

| RD2-seed19 = USLC

| RD2-team19 = Colorado Springs Switchbacks FC

| RD2-score19 = 0

| RD2-seed20 = USL1

| RD2-team20 = Northern Colorado Hailstorm FC

| RD2-score20 = 1*

| RD2-seed21 = USLC

| RD2-team21 = Birmingham Legion FC

| RD2-score21 = 2

| RD2-seed22 = NPSL

| RD2-team22 = Southern States Soccer Club

| RD2-score22 = 1

| RD2-seed23 = USLC

| RD2-team23 = Detroit City FC

| RD2-score23 = 3

| RD2-seed24 = NISA

| RD2-team24 = Michigan Stars FC

| RD2-score24 = 0

| RD2-seed25 = NISA

| RD2-team25 = California United Strikers FC

| RD2-score25 = 5

| RD2-seed26 = LQ

| RD2-team26 = San Fernando Valley FC

| RD2-score26 = 0

| RD2-seed27 = USLC

| RD2-team27 = El Paso Locomotive FC

| RD2-score27 = 1

| RD2-seed28 = USL1

| RD2-team28 = Central Valley Fuego FC

| RD2-score28 = 4

| RD2-seed29 = USL1

| RD2-team29 = Richmond Kickers

| RD2-score29 = 1

| RD2-seed30 = LQ

| RD2-team30 = Northern Virginia FC

| RD2-score30 = 0

| RD2-seed31 = USL1

| RD2-team31 = FC Tucson

| RD2-score31 = 3

| RD2-seed32 = USLC

| RD2-team32 = Las Vegas Lights FC

| RD2-score32 = 2

| RD2-seed33 = MLSNP

| RD2-team33 = Rochester New York FC

| RD2-score33 = 1

| RD2-seed34 = NAC

| RD2-team34 = Lansdowne Yonkers FC

| RD2-score34 = 0

| RD2-seed35 = USL1

| RD2-team35 = Greenville Triumph SC

| RD2-score35 = 2

| RD2-seed36 = USLC

| RD2-team36 = Oakland Roots SC

| RD2-score36 = 0

| RD2-seed37 = USL1

| RD2-team37 = Forward Madison FC

| RD2-score37 = 3

| RD2-seed38 = NPSL

| RD2-team38 = Cleveland SC

| RD2-score38 = 0

| RD2-seed39 = USLC

| RD2-team39 = Louisville City FC

| RD2-score39 = 1

| RD2-seed40 = USL1

| RD2-team40 = Chattanooga Red Wolves SC

| RD2-score40 = 0

| RD2-seed41 = USLC

| RD2-team41 = Miami FC

| RD2-score41 = 3

| RD2-seed42 = NPSL

| RD2-team42= Miami United FC

| RD2-score42 = 0

| RD2-seed43 = USL1

| RD2-team43 = North Carolina FC

| RD2-score43 = 1

| RD2-seed44 = USLC

| RD2-team44 = Rio Grande Valley FC

| RD2-score44 = 2

| RD2-seed45 = NISA

| RD2-team45 = Flower City Union

| RD2-score45 = 1*

| RD2-seed46 = USL2

| RD2-team46 = Western Mass Pioneers

| RD2-score46 = 0

| RD2-seed47 = USLC

| RD2-team47 = Orange County SC

| RD2-score47 = 5

| RD2-seed48 = NISA

| RD2-team48 = Los Angeles Force

| RD2-score48 = 2

| RD2-seed49 = USL1

| RD2-team49 = Union Omaha

| RD2-score49 = 2

| RD2-seed50 = USL2

| RD2-team50 = Des Moines Menace

| RD2-score50 = 1

| RD2-seed51 = USLC

| RD2-team51 = Phoenix Rising FC

| RD2-score51 = 1*

| RD2-seed52 = NISA

| RD2-team52 = Valley United FC

| RD2-score52 = 0

| RD2-seed53 = USLC

| RD2-team53 = FC Tulsa

| RD2-score53 = 2

| RD2-seed54 = NPSL

| RD2-team54 = Tulsa Athletic

| RD2-score54 = 1

| RD2-seed55 = USLC

| RD2-team55 = Pittsburgh Riverhounds SC

| RD2-score55 = 2

| RD2-seed56 = NISA

| RD2-team56 = Maryland Bobcats FC

| RD2-score56 = 0

| RD2-seed57 = USLC

| RD2-team57 = Sacramento Republic FC

| RD2-score57 = 6

| RD2-seed58 = USL2

| RD2-team58 = Portland Timbers U23s

| RD2-score58 = 0

| RD2-seed59 = MLSNP

| RD2-team59 = St. Louis City 2

| RD2-score59 = 2

| RD2-seed60 = USLC

| RD2-team60 = Indy Eleven

| RD2-score60 = 0

| RD2-seed61 = USLC

| RD2-team61 = New Mexico United

| RD2-score61 = 5

| RD2-seed62 = NPSL

| RD2-team62 = Las Vegas Legends

| RD2-score62 = 0

}}

Host team listed first

Bold = winner

* = after extra time, ( ) = penalty shootout score

All times local to game site.

{{Football box collapsible

|date = March 22

|time = 7:15 pm EDT

|team1 = Cleveland SC (NPSL) {{flagicon|Ohio}}

|score = 2–1

|aet = yes

|report = https://www.espn.com/soccer/match/_/gameId/631559

|team2 = {{flagicon|Illinois}} Chicago FC United (USL2)

|goals1 =

• Michael Derezic {{goal|90}}
• Vinny Bell {{goal|107}}

|goals2 =

• Mounir Alami {{goal|17}}

|stadium = George Finnie Stadium

|location = Berea, Ohio

|attendance = 250

|referee = Austin Saini

}}

{{Football box collapsible

|date = March 22

|time = 7:30 pm EDT

|team1 = Hartford City FC (NPSL) {{flagicon|Connecticut}}

|score = 0–3

|report = https://us.soccerway.com/matches/2022/03/23/united-states/us-open-cup/hartford-city/oyster-bay-united/3747729/

|team2 = {{flagicon|New York}} Oyster Bay United FC (LQ)

|goals1 =

|goals2 =

• Junior Rosero {{goal|16}}
• Franco Paz {{goal|32}}
• Sebastián Ruiz {{goal|45+2}}

|stadium = Trinity Health Stadium

|location = Hartford, Connecticut

|attendance = 200

|referee = Jeremy Scheer

}}

{{Football box collapsible

|date = March 22

|time = 7:30 pm EDT

|team1 = The Villages SC (USL2) {{flagicon|Florida}}

|score = 6–0

|report = https://us.soccerway.com/matches/2022/03/23/united-states/us-open-cup/the-villages/orlando-fc-wolves/3747731/

|team2 = {{flagicon|Florida}} Orlando FC Wolves (LQ)

|goals1 =

• Juan Felipe Rojas {{goal|12}}
• Rafael Vacas Barba {{goal|21||63}}
• Daniel Farias de Oliveira {{goal|41}}
• Jose Victor Rua France {{goal|57}}
• Payton Rausch {{goal|84}}

|goals2 =

|stadium = The Villages SC Complex

|location = Summerfield, Florida

|attendance = 225

|referee = Wesley Costa

}}

{{Football box collapsible

|date = March 22

|time = 7:30 pm CDT

|team1 = Denton Diablos FC (NPSL) {{flagicon|Texas}}

|score = 2–3

|report = https://us.soccerway.com/matches/2022/03/23/united-states/us-open-cup/denton-diablos/dfeeters-kicks/3747732/

|team2 = {{flagicon|Texas}} D'Feeters Kicks Soccer Club (LQ)

|goals1 =

• Julio Vargas {{goal|10}}
• Brandon Cerda {{goal|40}}
• Alejandro Estrada {{sentoff|0|70}}
• Carlos Flores {{sentoff|0|90+2}}

|goals2 =

• Sebastian Mendez {{goal|24}}
• Miles Byass {{goal|32}}
• Steven Chavez {{goal|45}}
• Adrian Renteria {{sentoff|0|54}}

|stadium = Mean Green Soccer Stadium

|location = Denton, Texas

|attendance = 100

|referee = Gloria Resendiz

}}

{{Football box collapsible

|date = March 22

|time = 7:30 pm CDT

|team1 = Southern States SC (NPSL) {{flagicon|Mississippi}}

|score = 3–1

|report = https://us.soccerway.com/matches/2022/03/23/united-states/us-open-cup/southern-states/georgia-revolution/3747733/

|team2 = {{flagicon|Georgia (U.S. state)}} Georgia Revolution FC (NPSL)

|goals1 =

• Jean Rivera {{goal|26}}
• Thomas Roy Shepherd {{goal|65||73}}

|goals2 =

• Karim Tmimi {{goal|82}}

|stadium = The Oakes

|location = Hattiesburg, Mississippi

|attendance = 300

|referee = Muhammad Hassan

}}

{{Football box collapsible

|date = March 23

|time = 2:45 pm PDT

|team1 = San Fernando Valley FC (LQ) {{flagicon|California}}

|score = 6–2

|report = https://us.soccerway.com/matches/2022/03/23/united-states/us-open-cup/san-fernando-valley/escondido-mayas/3747734/

|team2 = {{flagicon|California}} Escondido FC (LQ)

|goals1 =

• Tomas Bosuel {{goal|29||62||68}}
• Irvin Rivas {{goal|43}}
• Giancarlo Ponciano {{goal|47}}
• Ramiro Hermida {{goal|90}}

|goals2 =

• David A. Martín {{goal|45|pen.|79}}

|stadium = Sepulveda Basin Sports Complex

|location = Encino, California

|attendance = 100

|referee = Trevor Wiseman

}}

{{Football box collapsible

|date = March 23

|time = 7:00 pm EDT

|team1 = Ocean City Nor'easters (USL2) {{flagicon|New Jersey}}

|score = 1–1

|aet = yes

|team2 = {{flagicon|New York}} Lansdowne Yonkers FC (NAC)

|penaltyscore = 3–4

|goals1 = Pablo Da Silva Marquez {{goal|8}}, {{sent off|0|118}}

|goals2 = Shamir Mullings {{goal|12}}

|penalties1 =

• Adam Sternberger {{pengoal}}
• Kevin Curran {{penmiss}}
• Emanuel de Jesus Teixeira {{penmiss}}
• Nico Tramontana {{pengoal}}
• Kyle Galloway {{pengoal}}
• Leandro Tiago Louro da Silva {{penmiss}}

|penalties2 =

• Andrew Sousa {{pengoal}}
• Joseph Devivo {{pengoal}}
• Yohance Alexander {{penmiss}}
• Kyle Parish {{pengoal}}
• Johan Mauritzson {{penmiss}}
• Shamir Mullings {{pengoal}}

|stadium = Carey Stadium

|location = Ocean City, New Jersey

|attendance = 110

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:30 pm EDT

|team1 = South Carolina United FC (USL2) {{flagicon|South Carolina}}

|score = 0–1

|team2 = {{flagicon|North Carolina}} North Carolina Fusion U23 (USL2)

|goals1 =

|goals2 =

|stadium = SEFL Soccer Complex

|location = Columbia, South Carolina

|attendance =

|referee =

|note = South Carolina United forfeited the match after failing a pregame roster check, and the official result is a 1–0 win for North Carolina Fusion. The two teams elected to play a friendly, which ended in a 3–1 (aet) win for North Carolina.{{cite web |title=Nine More Teams Advance on Second Night of 2022 Lamar Hunt U.S. Open Cup First Round |url=https://www.ussoccer.com/stories/2022/03/nine-more-teams-advance-on-second-night-of-2022-lamar-hunt-us-open-cup-first-round |website=www.ussoccer.com |access-date=29 March 2022 |language=en |date=24 March 2022}}

}}

{{Football box collapsible

|date = March 23

|time = 7:30 pm EDT

|team1 = Miami United FC (NPSL) {{flagicon|Florida}}

|score = 3–1

|team2 = {{flagicon|Florida}} City Soccer FC (LQ)

|goals1 =

• Robertino Insúa {{goal|79}}
• Lucas Espindola {{goal|83||90+5|pen.}}

|goals2 =

• Oscar E. Reyes {{goal|82}}

|stadium = Ted Hendricks Stadium

|location = Hialeah, Florida

|attendance = 100

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:30 pm EDT

|team1 = Western Mass Pioneers (USL2) {{flagicon|Massachusetts}}

|score = 2–0

|team2 = {{flagicon|Massachusetts}} Brockton FC United (LQ)

|goals1 =

• Gabriel Vitalino Ganzer {{goal|48}}
• Joshua Calderón {{sent off|0|71}}
• Jacob Mannix {{goal|90+5}}

|goals2 =

• Rudney Delgado {{sent off|0|44}}

|stadium = Lusitano Stadium

|location = Ludlow, Massachusetts

|attendance = 200

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:00 pm CDT

|team1 = Des Moines Menace (USL2) {{flagicon|Iowa}}

|score = 4–2

|team2 = {{flagicon|Minnesota}} Minneapolis City SC (NPSL)

|goals1 =

• Maximiliano Galizzi {{goal|38}}
• William De Jesus Rodrigues {{goal|57}}
• Alessandro Salvadego {{goal|68||78}}

|goals2 =

• Lionel Vang {{goal|20}}
• Loïc Mesanvi {{goal|61}}

|stadium = Valley Stadium

|location = West Des Moines, Iowa

|attendance = 150

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:00 pm CDT

|team1 = Tulsa Athletic (NPSL) {{flagicon|Oklahoma}}

|score = 3–0

|team2 = {{flagicon|Colorado}} Azteca FC (LQ)

|goals1 =

• Aaron Ugbah {{goal|25}}
• Joseph Garcia {{goal|72|pen.}}
• Ruben Torres {{goal|75}}

|goals2 = Cesar Meza {{sent off|0|79}}

|stadium = Case Soccer Complex at ORU

|location = Tulsa, Oklahoma

|attendance = 350

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:00 pm PDT

|team1 = Portland Timbers U23s (USL2) {{flagicon|Oregon}}

|score = 2–1

|team2 = {{flagicon|California}} Contra Costa FC (LQ)

|goals1 =

• Thomas Petersen {{goal|51}}
• Eduardo Sanchez {{goal|51}}

|goals2 = Roberto González {{goal|90+2}}

|stadium = John Chambers Field

|location = Salem, Oregon

|attendance = 500

|referee =

}}

{{Football box collapsible

|date = March 23

|time = 7:00 pm PDT

|team1 = Las Vegas Legends (NPSL) {{flagicon|Nevada}}

|score = 3–2

|team2 = {{flagicon|Utah}} Park City Red Wolves SC (USL2)

|goals1 =

• Samuel Aina {{goal|10}}
• Brandon Vargas {{goal|34}}
• Roberto Soto {{goal|68}}

|goals2 =

• Leonardo Fuchs {{goal|84}}
• Kevin Jara-Collante {{goal|90+2}}

|stadium = Peter Johanan Soccer Field at UNLV

|location = Las Vegas, Nevada

|attendance = 724

|referee =

}}

{{Football box collapsible

|date = March 30

|time = 7:30 pm EDT

|team1 = Lynchburg FC (LQ) {{flagicon|Virginia}}

|score = 1–3

|team2 = {{flagicon|Virginia}} Northern Virginia FC (LQ)

|goals1 =

• Mitch Reed {{goal|25}}
• Bhayle Kearns {{sent off|0|90+2}}

|goals2 =

• Luke Campbell {{goal|13}}
• Jean-Philippe Ayolmbong {{goal|48}}
• Jhonny De Souza {{goal|85|pen.}} {{sent off|0|90+3}}

|stadium = Lynchburg City Stadium

|location = Lynchburg, Virginia

|attendance = 254

|referee =

|note =

}}

{{Football box collapsible

|date = April 1

|time = 7:00 pm EDT

|team1 = FC Motown (NPSL) {{flagicon|New Jersey}}

|score = 1–0

|aet =

|report =

|team2 = {{flagicon|Pennsylvania}} West Chester United SC (USL2)

|goals1 = Ryan Peterson {{goal|90+1}}

|goals2 =

|stadium = MSU Soccer Park

|location = Montclair, New Jersey

|attendance = 176

|referee =

|note = Match was originally played March 22 and resulted in a 2–3 (aet) win for West Chester. FC Motown lodged a protest, citing an illegal substitute made by West Chester, and won. The first result was nullified and the match will be replayed in its entirety.{{cite web |title=Public Statement by the Lamar Hunt U.S. Open Cup Adjudication & Discipline Panel |url=https://www.ussoccer.com/stories/2022/03/public-statement-by-the-lamar-hunt-us-open-cup-adjudication-and-discipline-panel |website=www.ussoccer.com |access-date=29 March 2022 |language=en |date=27 March 2022}}

}}

All times local to game site.

{{Football box collapsible

|date = April 5

|time = 7:00 pm EDT

|team1 = Charlotte Independence (USL1) {{flagicon|North Carolina}}

|score = 2–4

|team2 = {{flagicon|North Carolina}} North Carolina Fusion U23 (USL2)

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/charlotte-independence/carolina-dynamo/3755562/

|goals1 =

• Dutey {{goal|14}}
• Páez {{goal|41}}
• Mbuyu {{sentoff|0|70}}

|goals2 =

• Luis Neto {{goal|37}}
• João da Silva {{goal|51}}
• Marriott {{goal|88}}
• William Lorentz {{goal|90+5}}

|stadium = American Legion Memorial Stadium

|location = Charlotte, North Carolina

|attendance =

|referee = John Rush

}}

{{Football box collapsible

|date = April 5

|time = 7:00 pm EDT

|team1 = Pittsburgh Riverhounds SC (USLC) {{flagicon|Pennsylvania}}

|score = 2–0

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/pittsburgh-riverhounds/maryland-bobcats/3755524/

|team2 = {{flagicon|Maryland}} Maryland Bobcats FC (NISA)

|goals1 =

• Sims {{goal|37||55}}

|goals2 =

|stadium = Highmark Stadium

|location = Pittsburgh, Pennsylvania

|attendance =

|referee = Samuel Reynolds

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm EDT

|team1 = Indy Eleven (USLC) {{flagicon|Indiana}}

|score = 0–2

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/indy-eleven/st-louis-city-ii/3755669/

|team2 = {{flagicon|Missouri}} St. Louis City 2 (MLSNP)

|goals1 =

|goals2 =

• Armstrong {{goal|18}}
• Kuzain {{goal|72}}

|stadium = Carroll Stadium

|location = Indianapolis, Indiana

|attendance =

|referee = Carlos Rodriguez

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm EDT

|team1 = Detroit City FC (USLC) {{flagicon|Michigan}}

|score = 3–0

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/detroit-city/michigan-stars/3755516/

|team2 = {{flagicon|Michigan}} Michigan Stars FC (NISA)

|goals1 =

• Rutz {{goal|45}}
• Lewis {{goal|45+2||63}}

|goals2 =

|stadium = Keyworth Stadium

|location = Hamtramck, Michigan

|attendance =

|referee = Conlan Campbell

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm EDT

|team1 = Tampa Bay Rowdies (USLC) {{flagicon|Florida}}

|score = 6–0

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/fc-tampa-bay-rowdies/the-villages/3755535/

|team2 = {{flagicon|Florida}} The Villages SC (USL2)

|goals1 =

• Mkosana {{goal|12||20||53}}
• Scarlett {{goal|36}}
• LaCava {{goal|63}}
• Wyke {{goal|72}}

|goals2 =

|stadium = Al Lang Stadium

|location = St. Petersburg, Florida

|attendance =

|referee = Alex Billeter

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm CDT

|team1 = Union Omaha (USL1) {{flagicon|Nebraska}}

|score = 2–1

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/union-omaha/des-moines-menace/3755564/

|team2 = {{flagicon|Iowa}} Des Moines Menace (USL2)

|goals1 =

• Scearce {{goal|19}}
• Alfeu Bertini {{goal|81|o.g.}}

|goals2 =

• Hertzog {{goal|14}}

|stadium = Morrison Stadium

|location = Omaha, Nebraska

|attendance =

|referee = TJ Bartels

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm CDT

|team1 = FC Tulsa (USLC) {{flagicon|Oklahoma}}

|score = 2–1

|report = https://www.espn.com/soccer/match/_/gameId/632604

|team2 = {{flagicon|Oklahoma}} Tulsa Athletic (NPSL)

|goals1 =

• Brown {{goal|5}}
• Rodríguez {{goal|19}}

|goals2 =

• Billy Nzojyibwami {{goal|77}}

|stadium = ONEOK Field

|location = Tulsa, Oklahoma

|attendance = 2,388

|referee = Mathew Corrigan

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm CDT

|team1 = San Antonio FC (USLC) {{flagicon|Texas}}

|score = 3–1

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/san-antonio/dfeeters-kicks/3755534/

|team2 = {{flagicon|Texas}} D'Feeters Kicks Soccer Club (LQ)

|goals1 =

• Sakshaug {{goal|53||57}}
• Maloney {{goal|54}}

|goals2 =

• Sebastian Mendez {{goal|62}}
• Ramirez {{sentoff|0|83}}

|stadium = Toyota Field

|location = San Antonio, Texas

|attendance = 2,145

|referee = Elton Garcia

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm MDT

|team1 = New Mexico United (USLC) {{flagicon|New Mexico}}

|score = 5–0

|report = https://www.espn.com/soccer/scoreboard/_/league/USA.OPEN/date/20220405

|team2 = {{flagicon|Nevada}} Las Vegas Legends (NPSL)

|goals1 =

• Wehan {{goal|7|pen.}}
• Kiesewetter {{goal|17||86|pen.}}
• Ovouka {{goal|40}}
• Sainté {{goal|47}}

|goals2 =

• Guzman {{sentoff|0|82}}

|stadium = University of New Mexico Soccer Complex

|location = Albuquerque, New Mexico

|attendance = 2,128

|referee = Cuauhtemoc Delgadillo

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm PDT

|team1 = Central Valley Fuego FC (USL1) {{flagicon|California}}

|score = 4–1

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/central-valley-fuego/el-paso-locomotive/3755517/

|team2 = {{flagicon|Texas}} El Paso Locomotive FC (USLC)

|goals1 =

• Bijev {{goal|4||44}}
• Smith {{goal|15}}
• Chaney {{goal|62}}

|goals2 =

• John-Brown {{sentoff|0|58}}
• Calvillo {{goal|90}}

|stadium = Lamonica Stadium at Clovis High School

|location = Clovis, California

|attendance = 4,000

|referee = Michael Zapata

}}

{{Football box collapsible

|date = April 5

|time = 7:30 pm PDT

|team1 = Orange County SC (USLC) {{flagicon|California}}

|score = 5–2

|report = https://int.soccerway.com/matches/2022/04/06/united-states/us-open-cup/los-angeles-blues-sc/los-angeles-force/3755522/

|team2 = {{flagicon|California}} Los Angeles Force (NISA)

|goals1 =

• Pedersen {{goal|24}}
• Iloski {{goal|31}}
• Okoli {{goal|33}}
• Kuningas {{goal|53}}
• Henry {{goal|69}}

|goals2 =

• Goñi {{goal|37}}
• Clayton Torr {{goal|90}}

|stadium = Championship Soccer Stadium

|location = Irvine, California

|attendance =

|referee = Joseph Salinas

}}

{{Football box collapsible

|date = April 6

|time = 7:00 pm EDT

|team1 = FC Motown (NPSL) {{flagicon|New Jersey}}

|score = 1–0

|report = https://www.espn.com/soccer/match/_/gameId/632939

|team2 = {{flagicon|New York (state)}} AC Syracuse Pulse (NISA)

|aet = yes

|goals1 = Federico de Oliveira {{goal|96}}

|goals2 =

|stadium = MSU Soccer Park at Pittser Field

|location = Montclair, New Jersey

|attendance = 50

|referee = Luis Arroyo

}}

{{Football box collapsible

|date = April 6

|time = 7:00 pm EDT

|team1 = Miami FC (USLC) {{flagicon|Florida}}

|score = 3–0

|report = https://www.espn.com/soccer/match/_/gameId/632600

|team2 = {{flagicon|Florida}} Miami United FC (NPSL)

|goals1 = Murphy {{goal|12|pen.}}
Reid {{goal|30}}
Parkes {{goal|82}}

|goals2 =

|stadium = FIU Soccer Stadium

|location = Miami, Florida

|attendance = 527

|referee = Anya Voigt

}}

{{Football box collapsible

|date = April 6

|time = 7:00 pm EDT

|team1 = North Carolina FC (USL1) {{flagicon|North Carolina}}

|score = 1–2

|report = https://www.espn.com/soccer/match/_/gameId/632598

|team2 = {{flagicon|Texas}} Rio Grande Valley FC Toros (USLC)

|goals1 = Servania {{goal|45}}

|goals2 = López {{goal|54}}
Nodarse {{goal|79}}

|stadium = WakeMed Soccer Park

|location = Cary, North Carolina

|attendance = 575

|referee = John Rush

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm EDT

|team1 = Western Mass Pioneers (USL2) {{flagicon|Massachusetts}}

|score = 0–1

|report = https://www.espn.com/soccer/match/_/gameId/633419

|team2 = {{flagicon|New York (state)}} Flower City Union (NISA)

|aet = yes

|goals1 =

|goals2 = Fernandes {{goal|94}}
Marcus Micheletti {{sent off|0|110}}

|stadium = Lusitano Stadium

|location = Ludlow, Massachusetts

|attendance = 580

|referee = Jeremy Scheer

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm EDT

|team1 = Louisville City FC (USLC) {{flagicon|Kentucky}}

|score = 1–0

|report = https://www.loucity.com/news/2022/04/06/harris-nets-another-as-loucity-advances-in-the-open-cup/

|team2 = {{flagicon|Tennessee}} Chattanooga Red Wolves SC (USL1)

|goals1 = Harris {{goal|75}}

|goals2 =

|stadium = Lynn Family Stadium

|location = Louisville, Kentucky

|attendance = 4,520

|referee = Nabil Bensalah

}}

{{Football box collapsible

|date = April 6

|time = 8:00 pm EDT

|team1 = Northern Virginia FC (LQ) {{flagicon|Virginia}}

|score = 0–1

|report = https://us.soccerway.com/matches/2022/04/07/united-states/us-open-cup/evergreen/richmond-kickers/3755536/

|team2 = {{flagicon|Virginia}} Richmond Kickers (USL1)

|goals1 =

|goals2 = Olsen {{goal|34}}

|stadium = Virginia Revolution Sportsplex

|location = Leesburg, Virginia

|attendance = 575

|referee = Nicholas Karnovsky

}}

{{Football box collapsible

|date = April 6

|time = 7:00 pm CDT

|team1 = Forward Madison FC (USL1) {{flagicon|Wisconsin}}

|score = 3–0

|report = https://us.soccerway.com/matches/2022/04/07/united-states/us-open-cup/forward-madison/cleveland-sc/3755563/

|team2 = {{flagicon|Ohio}} Cleveland SC (NPSL)

|goals1 = Sukow {{goal|37}}
Murillo {{goal|45+1}}
Bartman {{goal|68}}

|goals2 =

|stadium = Breese Stevens Field

|location = Madison, Wisconsin

|attendance =

|referee = Calin Radosav

}}

{{Football box collapsible

|date = April 6

|time = 7:00 pm MDT

|team1 = Colorado Springs Switchbacks FC (USLC) {{flagicon|Colorado}}

|score = 0–1

|aet = yes

|report = https://us.soccerway.com/matches/2022/04/07/united-states/us-open-cup/colorado-springs/northern-colorado/3755515/

|team2 = {{flagicon|Colorado}} Northern Colorado Hailstorm FC (USL1)

|goals1 = Hodge {{sent off|2|90+6|103}}

|goals2 = Parra {{sent off|0|27}}
Jerry Desdunes {{goal|96}}

|stadium = Weidner Field

|location = Colorado Springs, Colorado

|attendance = 1,099

|referee = Laura Rodriguez

|note = First competitive game and goal for Northern Colorado.

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm MST

|team1 = FC Tucson (USL1) {{flagicon|Arizona}}

|score = 3–2

|report = https://us.soccerway.com/matches/2022/04/07/united-states/us-open-cup/fc-tucson/las-vegas-lights/3755518/

|team2 = {{flagicon|Nevada}} Las Vegas Lights FC (USLC)

|goals1 = Crull {{goal|45}}
Romero {{goal|71|o.g.}}
Allen {{goal|77}}

|goals2 = Traore {{goal|66}}
Crisostomo {{goal|80}}

|stadium = Kino North Stadium

|location = Tucson, Arizona

|attendance =

|referee = Benjamin Davis

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm MST

|team1 = Phoenix Rising FC (USLC) {{flagicon|Arizona}}

|score = 1–0

|aet = yes

|report = https://us.soccerway.com/matches/2022/04/07/united-states/us-open-cup/arizona-united/valley-united/3755523/

|team2 = {{flagicon|Arizona}} Valley United FC (NISA)

|goals1 = Repetto {{goal|115}}

|goals2 = Contreras {{sent off|0|81}}

|stadium = Wild Horse Pass Stadium

|location = Chandler, Arizona

|attendance =

|referee = Dejan Susak

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm PDT

|team1 = Albion San Diego (NISA) {{flagicon|California}}

|score = 1–2

|report = https://www.espn.com/soccer/match/_/gameId/632593

|team2 = {{flagicon|California}} San Diego Loyal SC (USLC)

|goals1 = Malango {{goal|65}}
Jacob Haupt {{sent off|0|90+2}}

|goals2 = Conway {{goal|45}}
Taylor Crull {{goal|89}}

|stadium = Canyon Crest Academy

|location = San Diego, California

|attendance = 1,750

|referee = Saul Rojas

}}

{{Football box collapsible

|date = April 6

|time = 7:30 pm PDT

|team1 = Bay Cities FC (NISA) {{flagicon|California}}

|score = 2–1

|report = https://www.espn.com/soccer/match/_/gameId/632612aa

|team2 = {{flagicon|California}} Monterey Bay FC (USLC)

|goals1 = Rei Dorwart {{goal|55}}
Edson Cardona {{goal|90+1}}

|goals2 = Crawford {{goal|87}}

|stadium = PayPal Park

|location = San Jose, California

|attendance = 1,083

|referee = Turan Özdemir

}}

{{Football box collapsible

|date = April 7

|time = 11:00 am EDT

|team1 = Charleston Battery (USLC) {{flagicon|South Carolina}}

|score = 0–1

|team2 = {{flagicon|Georgia (U.S. state)}} South Georgia Tormenta FC (USL1)

|goals1 =

|goals2 = Bosua {{goal|61}}

|stadium = Patriots Point Soccer Complex

|location = Mount Pleasant, South Carolina

|attendance = Played behind Closed Doors

|referee =

|note = Moved from April 6 due to extreme weather.

}}

{{Football box collapsible

|date = April 7

|time = 4:00 pm EDT

|team1 = Rochester New York FC (MLSNP) {{flagicon|New York (state)}}

|score = 1–0

|report= https://www.espn.com/soccer/match/_/gameId/632591

|team2 = {{flagicon|New York (state)}} Lansdowne Yonkers FC (NAC)

|goals1 = Rayo {{goal|45+5}}

|goals2 =

|stadium = John L. DiMarco Field at Monroe Community College

|location = Brighton, New York

|attendance = 267{{cite web |url=https://www.rhinos-archive.com/2022|title= 2022 Rochester New York FC Season|website=Rhinos Archive}}

|referee = Alex Parent

}}

{{Football box collapsible

|date = April 7

|time = 7:00 pm EDT

|team1 = Chattanooga FC (NISA) {{flagicon|Tennessee}}

|score = 3–1

|team2 = {{flagicon|Tennessee}} Memphis 901 FC (USLC)

|goals1 =

• Alex McGrath {{goal|1}}
• Ward {{goal|29}}
• Taylor Gray {{goal|45+3}}

|goals2 = Seagrist {{goal|39}}

|stadium = Finley Stadium

|location = Chattanooga, Tennessee

|attendance = 2,057

|referee = Wes Caouette

}}

{{Football box collapsible

|date = April 7

|time = 7:00 pm EDT

|team1 = Greenville Triumph SC (USL1) {{flagicon|South Carolina}}

|score = 2–0

|report=https://www.espn.com/soccer/match/_/gameId/632589

|team2 = {{flagicon|California}} Oakland Roots SC (USLC)

|goals1 =

• Keegan {{goal|29}}
• Smart {{goal|90+4}}

|goals2 =

|stadium = Legacy Early College Field

|location = Greenville, South Carolina

|attendance =

|referee = Wilmer Soriano

}}

{{Football box collapsible

|date = April 7

|time = 7:00 pm EDT

|report = https://us.soccerway.com/matches/2022/04/08/united-states/us-open-cup/hartford-athletic/oyster-bay-united/3755527/

|team1 = Hartford Athletic (USLC) {{flagicon|Connecticut}}

|score = 3–1

|team2 = {{flagicon|New York (state)}} Oyster Bay United FC (LQ)

|goals1 =

• Johnson {{goal|49}}
• Prpa {{goal|70}}
• Saydee {{goal|90+2}}

|goals2 = Junior Rosero {{goal|59|pen.}}

|stadium = Trinity Health Stadium

|location = Hartford, Connecticut

|attendance = 1,634

|referee = Kenneth Rojas

}}

{{Football box collapsible

|date = April 7

|time = 7:00 pm CDT

|team1 = Birmingham Legion FC (USLC) {{flagicon|Alabama}}

|score = 3–1

|team2 = {{flagicon|Mississippi}} Southern States SC (NPSL)

|goals1 =

• Kasim {{goal|48}}
• Lapa {{goal|62}}
• Marlon {{goal|63}}

|goals2 = Mason Walsh {{goal|73}}

|stadium = Alabama Soccer Stadium

|location = Tuscaloosa, Alabama

|attendance =

|referee = Benjamin Meyer

}}

{{Football box collapsible

|date = April 7

|time = 7:30 pm PDT

|team1 = California United Strikers FC (NISA) {{flagicon|California}}

|score = 5–0

|team2 = {{flagicon|California}} San Fernando Valley FC (LQ)

|goals1 =

• Marcus Lee {{goal|4}}
• Anthony López-Carrillo {{goal|15||78}}
• Aydan Bowers {{goal|31}}
• Guilherme Farias {{goal|71}}

|goals2 =

|stadium = Championship Soccer Stadium

|location = Irvine, California

|attendance =

|referee = Samantha Martinez

}}

{{Football box collapsible

|date = April 7

|time = 7:30 pm PDT

|team1 = Sacramento Republic FC (USLC) {{flagicon|California}}

|score = 6–0

|report= https://www.espn.com/soccer/match/_/gameId/632586

|team2 = {{flagicon|Oregon}} Portland Timbers U23s (USL2)

|goals1 =

• Lacroix {{goal|13||35}}
• Viader {{goal|22}}
• LaGrassa {{goal|26}}
• López {{goal|30}}
• Lewis {{goal|41}}

|goals2 =

|stadium = Heart Health Park

|location = Sacramento, California

|attendance = 2,260

|referee = Michael Zapata

}}

The winners of the second round and the new entrants to the tournament were grouped geographically into groups of four (12 groups) or six (eight groups), depending on the distribution of teams after the second round. Division I (MLS) teams entering the tournament were spread among the groups as evenly as possible (groups of four: five groups with two and seven groups with one MLS team; groups of six: one group with three and seven groups with two MLS teams). All MLS teams faced a lower-division team. Random selection for each group determined the pairs. Instances where geographical fit didn't exist when creating groups was resolved by random selection.

All times local to game site.

{{Football box collapsible

|date = April 19

|time = 7:00 pm EDT

|team1 = Miami FC (USLC) {{flagicon|Florida}}

|score = 0–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/miavsmia-04-19-2022/

|team2 = {{flagicon|Florida}} Inter Miami CF (MLS)

|goals1 =

|goals2 =

• Campana {{goal|83}}

|stadium = Riccardo Silva Stadium

|location = Miami, Florida

|attendance = 11,158

|referee = Alex Billeter

}}

{{Football box collapsible

|date = April 19

|time = 7:00 pm EDT

|team1 = Flower City Union (NISA) {{flagicon|New York}}

|score = 0–3

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/fcuvsdc-04-19-2022/

|team2 = {{flagicon|District of Columbia}} D.C. United (MLS)

|goals1 =

|goals2 =

• Kamara {{goal|73||86|pen.}}
• Robertha {{goal|81}}

|stadium = Rochester Community Sports Complex

|location = Rochester, New York

|attendance = 556{{cite web |url=https://www.rhinos-archive.com/fcu2022|title= Flower City Union 2022|website= Rhinos Archive}}

|referee = Luis Arroyo

}}

{{Football box collapsible

|date = April 19

|time = 7:00 pm EDT

|team1 = Detroit City FC (USLC) {{flagicon|Michigan}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/detvsclb-04-19-2022/

|team2 = {{flagicon|Ohio}} Columbus Crew (MLS)

|goals1 = Rodriguez {{goal|64||86|pen.}}

|goals2 = Zardes {{goal|7|pen.}}

|stadium = Keyworth Stadium

|location = Hamtramck, Michigan

|attendance = 6,121

|referee = Chris Ruska

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm EDT

|team1 = FC Cincinnati (MLS) {{flagicon|Ohio}}

|score = 2–0

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/cinvspit-04-19-2022/

|team2 = {{flagicon|Pennsylvania}} Pittsburgh Riverhounds SC (USLC)

|goals1 = Barreal {{goal|95|pen.|99}}

|goals2 =

|stadium = TQL Stadium

|location = Cincinnati, Ohio

|attendance = 5,458

|referee = Eric Tattersall

}}

{{Football box collapsible

|date = April 19

|time = 7:00 pm CDT

|team1 = Birmingham Legion FC (USLC) {{flagicon|Alabama}}

|score = 0–2

|report = https://int.soccerway.com/matches/2022/04/20/united-states/us-open-cup/birmingham-legion/tormenta/3778951/

|team2 = {{flagicon|Georgia (U.S. state)}} South Georgia Tormenta FC (USL1)

|goals1 =

|goals2 =

• Thorn {{goal|33}}
• Dengler {{goal|45}}

|stadium = Alabama Soccer Stadium

|location = Tuscaloosa, Alabama

|attendance =

|referee = Sergii Demianchuk

}}

{{Football box collapsible

|date = April 19

|time = 7:00 pm CDT

|team1 = Chicago Fire FC (MLS) {{flagicon|Illinois}}

|score = 2–2

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/chivsoma-04-19-2022/

|team2 = {{flagicon|Nebraska}} Union Omaha (USL1)

|penaltyscore = 4–5

|goals1 =

• Czichos {{goal|53|pen.}}, {{goal|115|pen.}}

|goals2 =

• Meza {{goal|68}}
• Touche {{goal|120+2}}

|stadium = Soldier Field

|location = Chicago, Illinois

|attendance =

|referee = Calin Radosav

|penalties1 =

• Przybyłko {{penmiss}}
• Czichos {{pengoal}}
• Espinoza {{pengoal}}
• Ivanov {{pengoal}}
• Bezerra {{pengoal}}
• Navarro {{penmiss}}

|penalties2 =

• {{pengoal}} Kametani
• {{pengoal}} Alihodžić
• {{penmiss}} Meza
• {{pengoal}} Knutson
• {{pengoal}} Montesdeoca
• {{pengoal}} Acoff

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm CDT

|team1 = FC Dallas (MLS) {{flagicon|Texas}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/dalvstul-04-19-2022/

|team2 = {{flagicon|Oklahoma}} FC Tulsa (USLC)

|goals1 =

• Jara {{goal|32|pen.}}
• Obrian {{goal|56}}

|goals2 = Bourgeois {{goal|42}}

|stadium = Toyota Stadium

|location = Frisco, Texas

|attendance = 2,287

|referee = Lorenzo Hernandez

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm CDT

|team1 = Houston Dynamo FC (MLS) {{flagicon|Texas}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/houvsrgv-04-19-2022/

|team2 = {{flagicon|Texas}} Rio Grande Valley FC (USLC)

|goals1 =

• Nodarse {{goal|9|o.g.}}
• Junqua {{goal|90+3}}

|goals2 = Hadebe {{goal|48|o.g.}}

|stadium = PNC Stadium

|location = Houston, Texas

|attendance = 7,983

|referee = Elton García

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm MST

|team1 = FC Tucson (USL1) {{flagicon|Arizona}}

|score = 1–2

|report = https://int.soccerway.com/matches/2022/04/20/united-states/us-open-cup/fc-tucson/california-utd-strikerrs/3778944/

|team2 = {{flagicon|California}} California United Strikers FC (NISA)

|goals1 = Calixtro {{goal|17}}

|goals2 =

• Nuño {{goal|71}}
• Kawashima {{goal|90+2}}

|stadium = Kino North Stadium

|location = Tucson, Arizona

|attendance = 528

|referee = Dejan Susak

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm PDT

|team1 = San Jose Earthquakes (MLS) {{flagicon|California}}

|score = 5–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/sjvsbay-04-19-2022/

|team2 = {{flagicon|California}} Bay Cities FC (NISA)

|goals1 =

• Skahan {{goal|25}}
• Marie {{goal|37}}
• Cowell {{goal|59|pen.}}
• Tsakiris {{goal|82}}
• Bouda {{goal|88}}

|goals2 =

|stadium = PayPal Park

|location = San Jose, California

|attendance = 8,058

|referee = Malik Badawi

}}

{{Football box collapsible

|date = April 19

|time = 7:30 pm PDT

|team1 = LA Galaxy (MLS) {{flagicon|California}}

|score = 1–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/lavssd-04-19-2022/

|team2 = {{flagicon|California}} San Diego Loyal SC (USLC)

|goals1 = Cabral {{goal|28}}

|goals2 =

|stadium = Dignity Health Sports Park

|location = Carson, California

|attendance = 9,473

|referee = Brandon Stevis

}}

{{Football box collapsible

|date = April 20

|time = 6:00 pm EDT

|report=|team1 = Rochester New York FC (MLSNP) {{flagicon|New York}}

|score = 2–2

|aet = yes

|penaltyscore = 4–3

|team2 = {{flagicon|New Jersey}} FC Motown (NPSL)

|goals1 = Batista {{goal|22}}
Inalien {{goal|39}}

|goals2 = Duka {{goal|40}}
Fala {{goal|90+1}}

|stadium = John L. DiMarco Field

|location = Brighton, New York

|attendance =396{{cite web |url=https://www.rhinos-archive.com/2022|title= 2022 Rochester New York FC Season|website=Rhinos Archive}}

|referee = Christian Centeno

|penalties1 =

• Rissi {{pengoal}}
• Williams {{penmiss}}
• Garrett {{penmiss}}
• Djaló {{pengoal}}
• Drai {{pengoal}}
• Vanacker {{pengoal}}

|penalties2 =

• {{penmiss}} Duka
• {{pengoal}} Fala
• {{pengoal}} Pieles
• {{penmiss}} de Oliveira
• {{pengoal}} Alberto
• {{penmiss}} Perez

}}

{{Football box collapsible

|date = April 20

|time = 6:30 pm EDT

|team1 = Richmond Kickers (USL1) {{flagicon|Virginia}}

|score = 1–0

|aet = yes

|team2 = {{flagicon|North Carolina}} North Carolina Fusion U23 (USL2)

|goals1 = Terzaghi {{goal|118}}

|goals2 =

|stadium = City Stadium

|location = Richmond, Virginia

|attendance = 1,219

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:00 pm EDT

|team1 = Hartford Athletic (USLC) {{flagicon|Connecticut}}

|score = 1–2

|team2 = {{flagicon|New Jersey}} New York Red Bulls (MLS)

|goals1 = McGlynn {{goal|51}}

|goals2 = Morgan {{goal|18}}
Long {{goal|25}}

|stadium = Trinity Health Stadium

|location = Hartford, Connecticut

|attendance = 5,144

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:00 pm EDT

|team1 = Orlando City SC (MLS) {{flagicon|Florida}}

|score = 2–1

|team2 = {{flagicon|Florida}} Tampa Bay Rowdies (USLC)

|goals1 = Pato {{goal|52}}
Urso {{goal|63}}

|goals2 = Mkosana {{goal|65}}

|stadium = Exploria Stadium

|location = Orlando, Florida

|attendance = 8,057

|referee =

|note = Game originally scheduled to be played at Osceola County Stadium in Kissimmee, Florida. Location changed on April 11.{{cite web |title=Orlando City SC’s Open Cup Match Against Tampa Bay Moved to Exploria Stadium |url=https://www.orlandocitysc.com/news/orlando-city-sc-s-open-cup-match-against-tampa-bay-moved-to-exploria-stadium |website=OrlandoCitySC.com |access-date=11 April 2022}}

}}

{{Football box collapsible

|date = April 20

|time = 7:00 pm EDT

|team1 = Greenville Triumph SC (USL1) {{flagicon|South Carolina}}

|score = 1–2

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/gvlvsclt-04-20-2022/stats

|team2 = {{flagicon|North Carolina}} Charlotte FC (MLS)

|goals1 = Keegan {{goal|59}}

|goals2 = Ortiz {{goal|39}}
Afful {{goal|105+1}}

|stadium = Legacy Early College Field

|location = Greenville, South Carolina

|attendance = 4,064

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 6:00 pm CDT

|report=|team1 = Forward Madison FC (USL1) {{flagicon|Wisconsin}}

|score = 0–2

|team2 = {{flagicon|Minnesota}} Minnesota United FC (MLS)

|goals1 =

|goals2 = Hunou {{goal|51}}
Kallman {{goal|83}}

|stadium = Breese Stevens Field

|location = Madison, Wisconsin

|attendance = 2,663

|referee = Jervis Atagana

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm EDT

|team1 = Atlanta United FC (MLS) {{flagicon|Georgia (U.S. state)}}

|score = 6–0

|team2 = {{flagicon|Tennessee}} Chattanooga FC (NISA)

|goals1 = Hernández {{goal|21}}
Dwyer {{goal|25||35}}
Moreno {{goal|53|pen.}}
Luiz Araújo {{goal|67}}
Lennon {{goal|84}}

|goals2 =

|stadium = Fifth Third Bank Stadium

|location = Kennesaw, Georgia

|attendance = 3,740

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm EDT

|team1 = Louisville City FC (USLC) {{flagicon|Kentucky}}

|report = https://us.soccerway.com/matches/2022/04/21/united-states/us-open-cup/louisville-city/st-louis-city-ii/3778937/

|score = 0–0

|aet = yes

|penaltyscore = 9–8

|team2 = {{flagicon|Missouri}} St. Louis City 2 (MLSNP)

|goals1 =

|goals2 =

|penalties1 =

• Totsch {{pengoal}}
• Harris {{pengoal}}
• Gonzalez {{penmiss}}
• Matsoso {{pengoal}}
• Moguel {{pengoal}}
• Pino {{pengoal}}
• Serrano {{pengoal}}
• Leinhos {{pengoal}}
• Gibson {{pengoal}}
• Wynder {{pengoal}}

|penalties2 =

• {{penmiss}} Schneider
• {{pengoal}} Di Rosa
• {{pengoal}} Hiebert
• {{pengoal}} Armstrong
• {{pengoal}} Yaro
• {{pengoal}} Rivas
• {{pengoal}} Heard
• {{pengoal}} Volmar
• {{pengoal}} Awuah
• {{penmiss}} Armstrong

|stadium = Lynn Family Stadium

|location = Louisville, Kentucky

|attendance = 5,243

|referee = Kyle Johnston

|note =

}}

{{Football box collapsible

|date = April 20

|time = 8:00 p.m. CDT

|team1 = San Antonio FC (USLC) {{flagicon|Texas}}

|score = 2–1

|aet = yes

|team2 = {{flagicon|Texas}} Austin FC (MLS)

|goals1 =

• Collier {{goal|82}}
• Manley {{goal|96}}

|goals2 = Fagúndez {{goal|47}}

|stadium = Toyota Field

|location = San Antonio, Texas

|attendance = 7,922

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm MDT

|team1 = Real Salt Lake (MLS) {{flagicon|Utah}}

|score = 0–1

|team2 = {{flagicon|Colorado}} Northern Colorado Hailstorm FC (USL1)

|goals1 =

|goals2 = Cornwall {{goal|70}}

|stadium = Rio Tinto Stadium

|location = Sandy, Utah

|attendance = 19,301

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm MST

|team1 = Phoenix Rising FC (USLC) {{flagicon|Arizona}}

|score = 2–1

|team2 = {{flagicon|New Mexico}} New Mexico United (USLC)

|goals1 =

• Calistri {{goal|6}}
• Hurst {{goal|81}}

|goals2 =

• Brett {{goal|65}}

|stadium = Wild Horse Pass Stadium

|location = Chandler, Arizona

|attendance =

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm PDT

|team1 = Sacramento Republic FC (USLC) {{flagicon|California}}

|score = 2–1

|team2 = {{flagicon|California}} Central Valley Fuego FC (USL1)

|goals1 =

• Casey {{goal|44}}
• López {{goal|90+5|pen.}}

|goals2 = Bustamante {{goal|76}}

|stadium = Heart Health Park

|location = Sacramento, California

|attendance = 3,712

|referee =

|note =

}}

{{Football box collapsible

|date = April 20

|time = 7:30 pm PDT

|report=|team1 = Los Angeles FC (MLS) {{flagicon|California}}

|score = 5–1

|team2 = {{flagicon|California}} Orange County SC (USLC)

|goals1 = Musovski {{goal|13||71}}
Arango {{goal|34||45}}
Jennings {{goal|68}}

|goals2 = Torres {{goal|73}}

|stadium = Banc of California Stadium

|location = Los Angeles, California

|attendance =

|referee =

|note =

}}

The winners of the Third Round and the new entrants to the tournament were grouped geographically into groups of four (eight groups). Each group had one of the MLS teams entering this round. Random selection for each group determined the pairs. Instances where geographical fit didn't exist when creating groups was resolved by random selection. The draw for the Round of 32 took place on April 21.{{Cite web |date=February 2, 2022 |title=2022 US Open Cup Handbook Finalists Edition |url=https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |url-status=live |access-date=April 21, 2022 |website=US Soccer|archive-url=https://web.archive.org/web/20220420172559/https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |archive-date=April 20, 2022 }}

All times local to game site.

{{Football box collapsible

|date = May 10

|time = 7:00 pm EDT

|team1 = Orlando City SC (MLS) {{flagicon|Florida}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/orlvsphi-05-10-2022/

|team2 = {{flagicon|Pennsylvania}} Philadelphia Union (MLS)

|goals1 = Kara {{goal|54}}
Perea {{goal|57}}

|goals2 = Findlay {{goal|77}}

|stadium = Exploria Stadium

|location = Orlando, Florida

|attendance = 7,601

|referee = Elvis Osmanovic

}}

{{Football box collapsible

|date = May 10

|time = 7:30 pm EDT

|team1 = D.C. United (MLS) {{flagicon|District of Columbia}}

|score = 0–3

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/dcvsrbny-05-10-2022/

|team2 = {{flagicon|New Jersey}} New York Red Bulls (MLS)

|goals1 =

|goals2 = Luquinhas {{goal|45+3}}
Tolkin {{goal|48}}
Ryan {{goal|68}}

|stadium = Audi Field

|location = Washington, D.C.

|attendance = 8,920

|referee = Matt Franz

}}

{{Football box collapsible

|date = May 10

|time = 7:30 pm EDT

|team1 = Detroit City FC (USLC) {{flagicon|Michigan}}

|score = 1–1

|aet = yes

|penaltyscore = 2–4

|report = https://us.soccerway.com/matches/2022/05/11/united-states/us-open-cup/detroit-city/louisville-city/3782744/

|team2 = {{flagicon|Kentucky}} Louisville City FC (USLC)

|goals1 = Rodriguez {{goal|14|pen.}}

|goals2 = Harris {{goal|24}}

|penalties1 =

• Rodriguez {{pengoal}}
• Williams {{penmiss}}
• Hoppenot {{pengoal}}
• Carroll {{penmiss}}

|penalties2 =

• {{pengoal}} Totsch
• {{pengoal}} McCabe
• {{pengoal}} Harris
• {{pengoal}} Pino

|stadium = Keyworth Stadium

|location = Hamtramck, Michigan

|attendance = 6,837

|referee = Calin Radosav

}}

{{Football box collapsible

|date = May 10

|time = 8:00 pm EDT

|team1 = Inter Miami CF (MLS) {{flagicon|Florida}}

|score = 3–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/miavstrm-05-10-2022/

|team2 = {{flagicon|Georgia (U.S. state)}} South Georgia Tormenta FC (USL1)

|goals1 = Lassiter {{goal|45||83}}
Robinson {{goal|47}}

|goals2 = Sterling {{goal|88}}

|stadium = DRV PNK Stadium

|location = Fort Lauderdale, Florida

|attendance = 3,198

|referee = Alejo Calume

}}

{{Football box collapsible

|date = May 10

|time = 7:30 pm CDT

|team1 = Sporting Kansas City (MLS) {{flagicon|Kansas}}

|score = 4–2

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/skcvsdal-05-10-2022/

|team2 = {{flagicon|Texas}} FC Dallas (MLS)

|goals1 = Vujnović {{goal|60}}
Tzionis {{goal|90+8}}
Cerrillo {{goal|94|o.g.}}
Shelton {{goal|113}}

|goals2 = Jara {{goal|8}}
Munjoma {{goal|34}}

|stadium = Children's Mercy Park

|location = Kansas City, Kansas

|attendance = 14,922

|referee = Malik Badawi

}}

{{Football box collapsible

|date = May 10

|time = 7:30 pm PDT

|team1 = Los Angeles FC (MLS) {{flagicon|California}}

|score = 2–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/lafcvspor-05-10-2022/

|team2 = {{flagicon|Oregon}} Portland Timbers (MLS)

|goals1 = Arango {{goal|32}}
Fall {{goal|54}}

|goals2 =

|stadium = Banc of California Stadium

|location = Los Angeles, California

|attendance = 11,014

|referee = Mark Allatin

}}

{{Football box collapsible

|date = May 11

|time = 6:30 pm EDT

|team1 = Richmond Kickers (USL1) {{flagicon|Virginia}}

|score = 1–5

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/rmkvsclt-05-11-2022/

|team2 = {{flagicon|North Carolina}} Charlotte FC (MLS)

|goals1 = Morán {{goal|53}}

|goals2 =

• Ríos {{goal|34}}
• Reyna {{goal|54}}
• Gaines {{goal|58||61}}
• Shinyashiki {{goal|86}}

|stadium = City Stadium

|location = Richmond, Virginia

|attendance = 4,621

|referee = Luis Arroyo

}}

{{Football box collapsible

|date = May 11

|time = 7:00 pm EDT

|team1 = New York City FC (MLS) {{flagicon|New York}}

|score = 3–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/nycvsroc-05-11-2022/

|team2 = {{flagicon|New York}} Rochester New York FC (MLSNP)

|goals1 =

• Thiago Andrade {{goal|23}}
• Héber {{goal|31}}
• Chanot {{goal|76}}

|goals2 =

• Batiz {{goal|45+3}}

|stadium = Belson Stadium

|location = New York, New York

|attendance =1,002

|referee = Ernie Constantine

}}

{{Football box collapsible

|date = May 11

|time = 7:00 pm EDT

|team1 = New England Revolution (MLS) {{flagicon|Massachusetts}}

|score = 5–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/nevscin-05-11-2022/

|team2 = {{flagicon|Ohio}} FC Cincinnati (MLS)

|goals1 = Gil {{goal|34|pen.|37||53}}
Buksa {{goal|47||57}}

|goals2 = Barreal {{goal|12}}

|stadium = Gillette Stadium

|location = Foxborough, Massachusetts

|attendance = 2,017

|referee = Lukasz Szpala

}}

{{Football box collapsible

|date = May 11

|time = 7:00 pm CDT

|team1 = Nashville SC (MLS) {{flagicon|Tennessee}}

|score = 3–2

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/nshvsatl-05-11-2022/

|team2 = {{flagicon|Georgia (U.S. state)}} Atlanta United FC (MLS)

|goals1 =

• Mukhtar {{goal|50|pen.}}
• Sapong {{goal|90+2}}
• Zubak {{goal|93}}

|goals2 =

• Almada {{goal|13}}
• Luiz Araújo {{goal|29}}

|stadium = Geodis Park

|location = Nashville, Tennessee

|attendance = 12,375

|referee = Elton García

}}

{{Football box collapsible

|date = May 11

|time = 7:00 pm CDT

|team1 = Union Omaha (USL1) {{flagicon|Nebraska}}

|score = 2–0

|report = https://us.soccerway.com/matches/2022/05/12/united-states/us-open-cup/union-omaha/northern-colorado/3782745/

|team2 = {{flagicon|Colorado}} Northern Colorado Hailstorm FC (USL1)

|goals1 =

• Meza {{goal|46}}
• Doyle {{goal|58}}

|goals2 =

|stadium = Al F. Caniglia Field

|location = Omaha, Nebraska

|attendance = 1,931

|referee = Esad Omanovic

}}

{{Football box collapsible

|date = May 11

|time = 7:30 pm CDT

|team1 = Houston Dynamo FC (MLS) {{flagicon|Texas}}

|score = 1–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/houvssa-05-11-2022/

|team2 = {{flagicon|Texas}} San Antonio FC (USLC)

|goals1 = Ferreira {{goal|82}}

|goals2 =

|stadium = PNC Stadium

|location = Houston, Texas

|attendance =2,541

|referee = Nima Saghafi

}}

{{Football box collapsible

|date = May 11

|time = 7:00 pm PDT

|team1 = Seattle Sounders FC (MLS) {{flagicon|Washington}}

|score = 2–2

|aet = yes

|penaltyscore = 9–10

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/seavssj-05-11-2022/

|team2 = {{flagicon|California}} San Jose Earthquakes (MLS)

|goals1 =

• Medranda {{goal|54}}
• Montero {{goal|77}}

|goals2 =

• Skahan {{goal|10|pen.}}
• Cowell {{goal|50}}

|stadium = Starfire Sports Complex

|location = Tukwila, Washington

|attendance = 3,773

|referee = Esad Omanovic

|penalties1 =

• Montero {{pengoal}}
• Cissoko {{pengoal}}
• Léo Chú {{penmiss}}
• Teves {{pengoal}}
• Adeniran {{pengoal}}
• Rowe {{pengoal}}
• Ragen {{pengoal}}
• Atencio {{pengoal}}
• Vargas {{pengoal}}
• Tolo {{pengoal}}
• Cleveland {{penmiss}}

|penalties2 =

• {{pengoal}} Espinoza
• {{penmiss}} Yueill
• {{pengoal}} Ebobisse
• {{pengoal}} Calvo
• {{pengoal}} Jamiro
• {{pengoal}} López
• {{pengoal}} Beason
• {{pengoal}} Skahan
• {{pengoal}} Ågren
• {{pengoal}} Remedi
• {{pengoal}} Bersano

}}

{{Football box collapsible

|date = May 11

|time = 7:30 pm PDT

|team1 = Sacramento Republic FC (USLC) {{flagicon|California}}

|score = 2–0

|report = https://us.soccerway.com/matches/2022/05/12/united-states/us-open-cup/sacramento-republic/arizona-united/3782747/

|team2 = {{flagicon|Arizona}} Phoenix Rising FC (USLC)

|goals1 =

• Luis Felipe {{goal|30}}
• Martínez {{goal|88}}

|goals2 =

|stadium = Heart Health Park

|location = Sacramento, California

|attendance = 3,273

|referee = Joseph Salinas

}}

{{Football box collapsible

|date = May 11

|time = 7:30 pm PDT

|team1 = California United Strikers FC (NISA) {{flagicon|California}}

|score = 2–3

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/cusvsla-05-11-2022/

|team2 = {{flagicon|California}} LA Galaxy (MLS)

|goals1 =

• Kadono {{goal|19}}
• Garcia-Lopez {{goal|87}}

|goals2 =

• Joveljić {{goal|45|pen.|83|pen.}}
• Lambe {{goal|80}}

|stadium = Championship Soccer Stadium

|location = Irvine, California

|attendance = 3,749

|referee = Samantha Martinez

}}

{{Football box collapsible

|date = May 12

|time = 1:00 pm CDT

|team1 = Minnesota United FC (MLS) {{flagicon|Minnesota}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/minvscol-05-12-2022/

|team2 = {{flagicon|Colorado}} Colorado Rapids (MLS)

|goals1 =

• Danladi {{goal|8}}
• Reynoso {{goal|87}}

|goals2 = Mezquida {{goal|15}}

|stadium = Allianz Field

|location = Saint Paul, Minnesota

|attendance =

|referee = Brandon Stevis

|note = Match was originally scheduled for May 11 and was suspended in the 20th minute due to lightning.{{cite web |url=https://www.startribune.com/minnesota-united-us-open-game-vs-colorado-rapids-suspended-bad-weather/600172551/ |title=Minnesota United's U.S. Open game vs. Colorado suspended because of bad weather |last=Volk |first=John |date=2022-05-12 |website=www.startribune.com |publisher=Star Tribune |location=Minneapolis, MN |access-date=2022-05-12 |url-status=live |archive-url=https://web.archive.org/web/20220512142447/https://www.startribune.com/minnesota-united-us-open-game-vs-colorado-rapids-suspended-bad-weather/600172551/ |archive-date=2022-05-12|df=mdy-all}}

}}

The winners of the Round of 32 were grouped geographically into groups of four (four groups). Random selection for each group determined the pairs. The Round of 16/Quarterfinal draw took place on May 12 at 8:30 PM EDT on Futbol Americas on ESPN+.{{Cite web |date=February 2, 2022 |title=2022 US Open Cup Handbook Finalists Edition |url=https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |url-status=live |access-date=April 21, 2022 |website=US Soccer|archive-url=https://web.archive.org/web/20220420172559/https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |archive-date=April 20, 2022 }}

{{16TeamBracket

| maxround =2

| seed-width = 40

| team-width = 165

| score-width = 30

| RD1 = Round of 16
May 24–25

| RD2 = Quarterfinals
June 21–22, 29

| RD1-group1 =Central

| RD1-seed1 =MLS

| RD1-team1 =Sporting Kansas City

| RD1-score1 =2

| RD1-seed2 =MLS

| RD1-team2 =Houston Dynamo FC

| RD1-score2 =1

| RD1-seed3 =MLS

| RD1-team3 =Minnesota United FC

| RD1-score3 =1

| RD1-seed4 =USL1

| RD1-team4 =Union Omaha

| RD1-score4 =2

| RD1-group2 = Northeast

| RD1-seed5 =MLS

| RD1-team5 =New York Red Bulls

| RD1-score5 =3

| RD1-seed6 =MLS

| RD1-team6 =Charlotte FC

| RD1-score6 =1

| RD1-seed7 =MLS

| RD1-team7 =New York City FC

| RD1-score7 =1*

| RD1-seed8 =MLS

| RD1-team8 =New England Revolution

| RD1-score8 =0

| RD1-group3 = Southeast

| RD1-seed9 =MLS

| RD1-team9 =Orlando City SC

| RD1-score9 =1 (4)

| RD1-seed10 =MLS

| RD1-team10 =Inter Miami CF

| RD1-score10 =1 (2)

| RD1-seed11 =USLC

| RD1-team11 =Louisville City FC

| RD1-score11 =1

| RD1-seed12 =MLS

| RD1-team12 =Nashville SC

| RD1-score12 =2

| RD1-group4 = West

| RD1-seed13 =MLS

| RD1-team13 =LA Galaxy

| RD1-score13 =3

| RD1-seed14 =MLS

| RD1-team14 =Los Angeles FC

| RD1-score14 =1

| RD1-seed15 =USLC

| RD1-team15 =Sacramento Republic FC

| RD1-score15 =2

| RD1-seed16 =MLS

| RD1-team16 =San Jose Earthquakes

| RD1-score16 =0

| RD2-seed1 =MLS

| RD2-team1 =Sporting Kansas City

| RD2-score1 =6

| RD2-seed2 =USL1

| RD2-team2 =Union Omaha

| RD2-score2 =0

| RD2-seed3 =MLS

| RD2-team3 =New York Red Bulls

| RD2-score3 =3

| RD2-seed4 =MLS

| RD2-team4 =New York City FC

| RD2-score4 =0

| RD2-seed5 =MLS

| RD2-team5 =Orlando City SC

| RD2-score5 =1 (6)

| RD2-seed6 =MLS

| RD2-team6 =Nashville SC

| RD2-score6 =1 (5)

| RD2-seed7 =MLS

| RD2-team7 =LA Galaxy

| RD2-score7 = 1

| RD2-seed8 =USLC

| RD2-team8 = Sacramento Republic FC

| RD2-score8 =2

}}

Bold = winner

* = after extra time, ( ) = penalty shoot-out score

All times local to game site.

{{Football box collapsible

|date = May 25

|time = 7:00 pm EDT

|team1 = Orlando City SC (MLS) {{flagicon|Florida}}

|score = 1–1

|aet = yes

|penalties1 =

• Kara {{pengoal}}
• Jansson {{pengoal}}
• Perea {{pengoal}}
• Pereyra {{pengoal}}

|penaltyscore = 4–2

|penalties2 =

• {{pengoal}} Campana
• {{penmiss}} Duke
• {{penmiss}} Yedlin
• {{pengoal}} Lassiter

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/orlvsmia-05-25-2022/

|team2 = {{flagicon|Florida}} Inter Miami CF (MLS)

|goals1 =

• Torres {{goal|97}}

|goals2 =

• Mota {{goal|94}}

|stadium = Exploria Stadium

|location = Orlando, Florida

|attendance = 11,509

|referee = Kevin Broadley

}}

{{Football box collapsible

|date = May 25

|time = 7:00 pm EDT

|team1 = Louisville City FC (USLC) {{flagicon|Kentucky}}

|score = 1–2

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/louvsnsh-05-25-2022/

|team2 = {{flagicon|Tennessee}} Nashville SC (MLS)

|goals1 = *Ownby {{goal|37}}

|goals2 =

• Loba {{goal|39}}
• Mukhtar {{goal|89}}

|stadium = Lynn Family Stadium

|location = Louisville, Kentucky

|attendance = 8,638

|referee = Eric Tatersall

}}

{{Football box collapsible

|date = May 25

|time = 7:30 pm EDT

|team1 = New York City FC (MLS) {{flagicon|New York}}

|score = 1–0

|aet = yes

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/nycvsne-05-25-2022/

|team2 = {{flagicon|Massachusetts}} New England Revolution (MLS)

|goals1 =

• Rodríguez {{goal|94}}

|goals2 =

|stadium = Belson Stadium

|location = New York, New York

|attendance =1,200

|referee = Luis Arroyo

}}

{{Football box collapsible

|date = May 25

|time = 8:00 pm EDT

|team1 = New York Red Bulls (MLS) {{flagicon|New Jersey}}

|score = 3–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/rbnyvsclt-05-25-2022/

|team2 = {{flagicon|North Carolina}} Charlotte FC (MLS)

|goals1 =

• Klimala {{goal|2}}
• Nealis {{goal|63}}
• Barlow {{goal|90+2}}

|goals2 =

• Ríos {{goal|8}}

|stadium = MSU Soccer Park

|location = Montclair, New Jersey

|attendance = 3,500

|referee = Ernie Constantine

}}

{{Football box collapsible

|date = May 25

|time = 7:00 pm CDT

|team1 = Minnesota United FC (MLS) {{flagicon|Minnesota}}

|score = 1–2

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/minvsoma-05-25-2022/

|team2 = {{flagicon|Nebraska}} Union Omaha (USL1)

|goals1 =

• Hunou {{goal|6}}

|goals2 =

• Kametani {{goal|45+1}}
• Brito {{goal|51}}

|stadium = Allianz Field

|location = Saint Paul, Minnesota

|attendance =

|referee = Elton García

}}

{{Football box collapsible

|date = May 25

|time = 7:30 pm CDT

|team1 = Sporting Kansas City (MLS) {{flagicon|Kansas}}

|score = 2–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/skcvshou-05-25-2022/

|team2 = {{flagicon|Texas}} Houston Dynamo FC (MLS)

|goals1 =

• Russell {{goal|52||73|pen.}}

|goals2 =

• Baird {{goal|41}}

|stadium = Children's Mercy Park

|location = Kansas City, Kansas

|attendance = 14,913

|referee = Calin Radosav

}}

{{Football box collapsible

|date = May 25

|time = 7:30 pm PDT

|team1 = LA Galaxy (MLS) {{flagicon|California}}

|score = 3–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/lavslafc-05-25-2022/

|team2 = {{flagicon|California}} Los Angeles FC (MLS)

|goals1 =

• Cabral {{goal|51}}
• Hernández {{goal|57}}
• Joveljić {{goal|81}}

|goals2 =

• Hollingshead {{goal|85}}

|stadium = Dignity Health Sports Park

|location = Carson, California

|attendance = 24,174

|referee = Brandon Stevis

}}

{{Football box collapsible

|date = May 25

|time = 7:30 pm PDT

|team1 = Sacramento Republic FC (USLC) {{flagicon|California}}

|score = 2–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/sacvssj-05-25-2022/

|team2 = {{flagicon|California}} San Jose Earthquakes (MLS)

|goals1 =

• Luis Felipe {{goal|28}}
• López {{goal|83}}

|goals2 =

|stadium = Heart Health Park

|location = Sacramento, California

|attendance = 11,569

|referee = Elijio Arreguin

}}

All times local to game site.

{{Football box collapsible

|date = June 21

|time = 7:30 pm PDT

|team1 = LA Galaxy (MLS) {{flagicon|California}}

|score = 1–2

|report =https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/lavssac-06-21-2022/

|team2 = {{flagicon|California}} Sacramento Republic FC (USLC)

|goals1 =

• Donovan {{goal|18|o.g.}}

|goals2 =

• López {{goal|4}}
• Luis Felipe {{goal|70}}

|stadium = Dignity Health Sports Park

|location = Carson, California

|attendance = 12,315

|referee = Malik Badawi

}}

{{Football box collapsible

|date = June 22

|time = 7:00 pm EDT

|team1 = New York Red Bulls (MLS) {{flagicon|New Jersey}}

|score = 3–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/rbnyvsnyc-06-22-2022/

|team2 = {{flagicon|New York}} New York City FC (MLS)

|goals1 =

• Morgan {{goal|52}}
• Luquinhas {{goal|70}}
• Fernandez {{goal|90+1}}

|goals2 =

|stadium = Red Bull Arena

|location = Harrison, New Jersey

|attendance = 12,575

|referee = Matthew Thompson

}}

{{Football box collapsible

|date = June 22

|time = 7:30 pm CDT

|team1 = Sporting Kansas City (MLS) {{flagicon|Kansas}}

|score = 6–0

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/skcvsoma-06-22-2022/

|team2 = {{flagicon|Nebraska}} Union Omaha (USL1)

|goals1 =

• Sallói {{goal|10||53}}
• Ford {{goal|37}}
• Shelton {{goal|56}}
• Hernández {{goal|66||81}}

|goals2 =

|stadium = Children's Mercy Park

|location = Kansas City, Kansas

|attendance = 18,552

|referee = Brandon Stevis

}}

{{Football box collapsible

|date = June 29

|time = 7:00 pm EDT

|team1 = Orlando City SC (MLS) {{flagicon|Florida}}

|score =1–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/orlvsnsh-06-29-2022/

|team2 = {{flagicon|Tennessee}} Nashville SC (MLS)

|goals1 =Schlegel {{goal|90+4}}

|goals2 =*Mukhtar {{goal|52}}

|stadium = Exploria Stadium

|aet=yes|location = Orlando, Florida

|attendance =11,940

|referee =Mark Allatin

|penalties1=*Kara {{pengoal}}

• Jansson {{pengoal}}
• Perea {{penmiss}}
• Smith {{pengoal}}
• Pato {{pengoal}}
• Carlos {{pengoal}}
• Torres {{pengoal}}|penaltyscore=6–5|penalties2=*{{penmiss}} Muyl
• {{pengoal}} Loba
• {{pengoal}} Maher
• {{pengoal}} Zimmerman
• {{pengoal}} Zubak
• {{pengoal}} Romney
• {{penmiss}} Miller}}

The Quarterfinal winners were matched geographically to determine the pairings for the semifinal round. The draw to determine the home teams for the semifinals and the final was held on June 23.{{Cite web |date=February 2, 2022 |title=2022 US Open Cup Handbook Finalists Edition |url=https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |url-status=live |access-date=April 21, 2022 |website=US Soccer|archive-url=https://web.archive.org/web/20220420172559/https://cdn.ussoccer.com/-/media/project/ussf/open-cup/2022/2022opencuphandbookfinalistsedition-v120220202.ashx?la=en-us&rev=17e94fe0967445919973f80a3e3dcb00 |archive-date=April 20, 2022 }}

{{4TeamBracket

| seed-width = 40

| team-width = 165

| score-width = 35

| RD1 = Semifinals
July 27

| RD2 = Final
September 7

| RD1-seed1 = MLS

| RD1-team1 = Orlando City SC

| RD1-score1 = 5

| RD1-seed2 = MLS

| RD1-team2 = New York Red Bulls

| RD1-score2 = 1

| RD1-seed3 = USLC

| RD1-team3 = Sacramento Republic FC

| RD1-score3 =0 (5)

| RD1-seed4 = MLS

| RD1-team4 = Sporting Kansas City

| RD1-score4 =0 (4)

| RD2-seed1 = MLS

| RD2-team1 = Orlando City SC

| RD2-score1 = 3

| RD2-seed2 = USLC

| RD2-team2 =Sacramento Republic FC

| RD2-score2 = 0

}}

All times local to game site.

{{Football box collapsible

|date = July 27

|time = 7:30 pm EDT

|team1 = Orlando City SC (MLS) {{flagicon|Florida}}

|score = 5–1

|report = https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/orlvsrbny-07-27-2022/

|team2 = {{flagicon|New Jersey}} New York Red Bulls (MLS)

|goals1 =

• Araújo {{goal|45+5||62}}
• Pereyra {{goal|47}}
• Torres {{goal|75}}
• Michel {{goal|83}}

|goals2 =

• Morgan {{goal|45+1}}

|stadium = Exploria Stadium

|location = Orlando, Florida

|attendance = 11,612

|referee = Victor Rivas

}}

{{Football box collapsible

|date = July 27

|time = 7:30 pm PDT

|team1 = Sacramento Republic FC (USLC) {{flagicon|California}}

|score =0–0

|report =https://www.mlssoccer.com/competitions/u-s-open-cup/2022/matches/sacvsskc-07-27-2022/

|team2 = {{flagicon|Kansas}} Sporting Kansas City (MLS)

|goals1 =

|goals2 =

|stadium = Heart Health Park

|aet=yes|location = Sacramento, California

|attendance = 11,569{{cite web |title=Recap: Sporting suffers heartbreaking shootout loss to Sacramento in Open Cup semifinals |url=https://www.sportingkc.com/news/recap-sporting-suffers-heartbreaking-shootout-loss-to-sacramento-in-open-cup-sem |website=SportingKC.com |access-date=28 July 2022}}

|referee = Allen Chapman

|penalties1=

• Viader {{pengoal}}
• Fernandes {{pengoal}}
• Archimède {{pengoal}}
• Foster {{pengoal}}
• López {{pengoal}}

|penaltyscore=5–4

|penalties2=

• {{pengoal}} Russell
• {{pengoal}} Sallói
• {{pengoal}} Agada
• {{pengoal}} Hernández
• {{penmiss}} Zusi}}

{{main|2022 U.S. Open Cup final}}

{{:2022 U.S. Open Cup final}}

{{legend|silver|Team eliminated for this round.}}

First Round matches were split between ESPN+ and U.S. Soccer's YouTube channel; all matches from the second round to the final were broadcast on ESPN+. This is the final year of a four-year agreement between ESPN and U.S. Soccer to broadcast the tournament. Warner Bros. Discovery Sports will have the rights starting in 2023, as part of an 8-year agreement with U.S. Soccer.

{{reflist}}

{{U.S. Open Cup}}

{{2022 in American men's soccer}}

{{2021–22 in North and Central America, and Caribbean football (CONCACAF)}}

{{2022–23 in North and Central America, and Caribbean football (CONCACAF)}}

Category:U.S. Open Cup

Category:2022 in American soccer

Category:2022 North American domestic association football cups

Category:2022 domestic association football cups