In 1840 General Walker Keith Armistead, commander at that time of United States troops in the Second Seminole War, ordered construction of a hospital on the island. U.S. Army headquarters for the war in Florida were moved to the island, and it became known as Depot Key.
Worth, commander of the U.S. Army in Florida, met with Seminole leaders on Depot Key and negotiated an agreement that if the Seminoles retreated to southernmost Florida and stayed there the Army would leave them be. On the basis of this agreement, Colonel Worth declared the Second Seminole War to be over.