The dangerous shoals and reefs near the Dry Tortugas have destroyed hundreds of ships, leaving a long legacy of shipwrecks, strandings, and fatalities.  Because of the development of commerce among the Gulf port cities, these well traveled waters were a treacherous hazard to vessels.  The Lighthouse Board announced that a lighthouse on Garden Key would be one the most important navigational aids in the United States.

The first lighthouse on Garden Key was established in 1825, shortly after Florida became a US territory.  The barren island provided only brush and grass, so the lighthouse keepers set about planting vegetables and coconut trees to help tide them over between supply ships.  They led a lonely and isolated life until 1846, when the U.S. Army set its sights on building an imposing military fortification on the island.

Known as the "Gibraltar of the Gulf", Fort Jefferson’s construction began in 1846, using the workforce of slaves, Union Army deserters and Confederate war prisoners.  Despite the 30 years of labor, the massive hexagonal fort was never completed.  This light, along with the Loggerhead Key light, was one of the only Gulf Coast towers staying in full operation throughout the Civil War.

Following a powerful hurricane in 1873 and a fever outbreak, the U.S. Army withdrew its forces from Fort Jefferson and converted the stronghold into a prison for deserters and criminals.  The fort's most famous prisoner was Doctor Samuel Mudd, who had set the broken leg of John Wilkes Booth after he killed President Abraham Lincoln.

In 1876, the Lighthouse Board realized that mariners needed a new beacon at this strategic site because the first lighthouse, which was damaged from a hurricane, had been downgraded to a fourth-class harbor light.  Officials commissioned a new Fort Jefferson light 93 feet away from the original structure with a kerosene-powered Fourth Order Fresnel lens.  The new 37-foot iron tower was built at the top of a 50 foot high parapet in the fort walls.

In 1912 the lightstation was automated, replacing the butts of kerosene with tanks of compressed acetylene to fuel the beacon.  It continued in operation for 12 additional years until being decommissioned in 1924.