The lighthouse and its outbuildings were the only structures on Garden Key until construction started on Fort Jefferson in 1846.
The Garden Key lighthouse received a fourth-order Fresnel lens and became the harbor light for Fort Jefferson.
In 1912, the keeper's house burned down, and the lighthouse was automated with tanks of compressed acetylene replacing the butts of kerosene to fuel the lights.
USS Maine was part of the squadron stationed at Garden Key when it exploded and sank in the harbor of Havana, Cuba.
James Fenimore Cooper's 1848 novel Jack Tier: or the Florida Reefs, is set at the Garden Key lighthouse.