He was the son of Grand Duke Louis I of Hesse and his consort Louise of Hesse-Darmstadt. In 1833, he married Wilhelmine of Baden, youngest daughter of Charles Louis, Hereditary Prince of Baden and Amalia of Hesse-Darmstadt.
Wilhelmine bore him seven children, of whom four survived. Their last four children, including en:Alexander of Hesse-Darmstadt and en:Maria Alexandrovna of Hesse, were believed to have been fathered by en:August von Senarclens de Grancy, her longtime lover.
- Prince Ludwig of Hesse-Darmstadt (1806-1877); (the future grand duke)
- Prince Karl Wilhelm Ludwig of Hesse-Darmstadt (1809-1877)
- Unnamed Infant (born & died 1820)
- Princess Amalia Elisabeth Luise Karoline Friederike Wilhelmine of Hesse-Darmstadt (1821-1826)
- Prince Alexander Ludwig Georg Friedrich Emil of Hesse-Darmstadt (1823-1888)
- Princess Maximiliane Wilhelmine Auguste Sophie Marie of Hesse-Darmstadt (1824-1880); the future Empress consort of Tsar Alexander II of Russia.