[2] In 1733, 19 ships of the Spanish treasure fleet were wrecked on the nearby Florida Reef off of Hawk Channel by a hurricane; some of the survivors camped on Indian Key until they were rescued.

Beginning in the 18th century, Bahamians and Cubans used Indian Key as a base for fishing, turtling, logging, and wrecking.

He moved to Indian Key in 1830, began buying property on the island, and soon became the leader of the community and its chief landlord.

As a result of lobbying by Housman, Indian Key acquired an Inspector of Customs in 1832 and a post office in 1834.

The dead included Dr. Henry Perrine, former United States Consul in Campeche, Mexico, who was waiting at Indian Key until it was safe to take up a 36 sq mi (93 km2) grant on the mainland that Congress had awarded to him.

[13][14][15] The naval base on Tea Table Key had been stripped of personnel for an operation on the southwest coast of the mainland, leaving only the doctor, his patients, and five sailors under a midshipman to look after them.

The Keys lost most of their population again during the Civil War, but William Bethel, a wrecker, continued to live on the island from the 1850s until sometime after 1880.