Missouri Route 221
{{Short description|State highway in Missouri}}
{{Use American English|date=April 2025}}
{{Use mdy dates|date=January 2025}}
{{Infobox road
|state=MO
|type=Route
|route=221
|maint=MoDOT
| map={{maplink-road|from=Missouri Route 221.map}}
|map_custom=yes
|map_notes=MO 221 highlighted in red
|length_mi=16.317
|length_km=
|length_round=
|length_ref={{MoDOT Flex|accessdate=2013-02-15}}
|established={{circa|2010–2012}}
|direction_a=West
|terminus_a={{Jct|state=MO|Route|21}} near Pilot Knob
|junction=
|direction_b=East
|terminus_b={{Jct|state=MO|US|67}} near Farmington
|previous_type=Route
|previous_route=215
|next_type=Route
|next_route=224
|counties=Iron, St. Francois
}}
Route 221 is a {{convert|16.317|mi|km|adj=mid|-long}} east–west highway in eastern Missouri. Its western terminus is at Route 21 near Pilot Knob. Its eastern terminus is at U.S. Route 67 (US 67) near Farmington.
Major intersections
{{Jcttop|state=MO|length_ref=}}
{{MOint
|county=Iron
|location=none
|mile=0.000
|road={{Jct|state=MO|Route|21}}
}}
{{MOint
|county=St. Francois
|cspan=3
|location=none
|mile=9.040
|road={{Jct|state=MO|Supp|NN}}
}}
{{MOint
|location=Doe Run
|mile=12.744
|road={{Jct|state=MO|Supp|B}}
}}
{{MOint
|location=none
|mile=16.140
|mile2=16.317
|road={{Jct|state=MO|US|67|Supp|W}}
|notes=Diverging diamond interchange, existing interchange converted September 2012{{ cite press release | publisher = Missouri Department of Transportation | author = Southeast District | title = Route 221 to Close for Interchange Conversion in St. Francois County | url = http://www.modot.org/southeast/news_and_information/District10Release.shtml?action=displaySSI&newsId=174477 | date = August 17, 2012 | accessdate = April 8, 2014 }}
}}
{{Jctbtm}}