She married Frederick V, Landgrave of Hesse-Homburg on 27 September 1768. The marriage was contracted for diplomatic and political reasons as the symbol of an inheritance dispute between their respective families. Caroline and Frederick V produced many children but their marriage never developed into a personal relationship, and they lived mostly separated lives. Caroline often spent time in her villa in the forest near Homburg.

Issue

Frederick VI, Landgrave of Hesse-Homburg (1769–1829), married Princess Elizabeth of the United Kingdom (1770–1840)
Louis William (1770–1839), married Princess Augusta of Nassau-Usingen (1778–1846), divorced in 1805
Caroline (1771–1854), married Prince Louis Frederick II, Prince of Schwarzburg-Rudolstadt (1767–1807)
Louise Ulrike (1772–1854), married Prince Charles Günther of Schwarzburg-Rudolstadt (1771–1825)
Amalie (1774–1846), married Frederick, Hereditary Prince of Anhalt-Dessau (1769–1814)
Auguste (1776–1871), married Frederick Louis, Hereditary Grand Duke of Mecklenburg-Schwerin (1778–1819)
Philip (1779–1846), married Rosalie Antonie, Countess of Naumburg, Baroness Schimmelpenninck von der Oye, née Pototschnig (1806–1845)
Gustav (1781–1848), married Princess Louise of Anhalt-Dessau (1798–1858)
Ferdinand (1783–1866), the last Landgrave of Hesse-Homburg
Maria Anna (1785–1846) married Prince Wilhelm of Prussia (1783–1851)
Leopold (1787–1813), fell in the Battle of Großgörschen

Ancestry

{{ahnentafel

|collapsed=yes |align=center |ref={{cite book|title=Genealogie ascendante jusqu'au quatrieme degre inclusivement de tous les Rois et Princes de maisons souveraines de l'Europe actuellement vivans| trans-title=Genealogy up to the fourth degree inclusive of all the Kings and Princes of sovereign houses of Europe currently living |url=https://books.google.com/books?id=AINPAAAAcAAJ&pg=PA69|year=1768|publisher=Frederic Guillaume Birnstiel|location=Bourdeaux|language=fr|page=69}}

|boxstyle_1=background-color: #fcc;

|boxstyle_2=background-color: #fb9;

|boxstyle_3=background-color: #ffc;

|boxstyle_4=background-color: #bfc;

|1= 1. Caroline of Hesse-Darmstadt

|2= 2. Louis IX, Landgrave of Hesse-Darmstadt

|3= 3. Countess Palatine Caroline of Zweibrücken

|4= 4. Louis VIII, Landgrave of Hesse-Darmstadt

|5= 5. Countess Charlotte of Hanau-Lichtenberg

|6= 6. Christian III, Count Palatine of Zweibrücken

|7= 7. Caroline of Nassau-Saarbrücken

|8= 8. Ernest Louis, Landgrave of Hesse-Darmstadt