He was the fourth (but third surviving) son of Frederick Erdmann, Prince of Anhalt-Pless, by his wife, Louise Ferdinande, daughter of Henry Ernest, Count of Stolberg-Wernigerode.

After his elder brother Frederick Ferdinand inherited Anhalt-Köthen in 1818, Henry assumed the government over the state country of Pless.

In 1821, he took under his protection its creator, Samuel Hahnemann, who remained with his large family in Köthen for the next fourteen years as Henry's physician.

On his death, the duchy was inherited by his kinsmen Alexander Karl of Anhalt-Bernburg and Leopold IV of Anhalt-Dessau.

However, Alexander renounced his rights over Köthen on behalf of Leopold IV since it was clear that his eventual assumption of all the Anhalt lands was inevitable.