The Florida Superintendency was formally established in 1822, but officials had been assigned to Florida the previous year. Until the establishment of the Bureau of Indian Affairs in 1824, the superintendency was under the direct supervision of the secretary of war. The territorial governor, who resided permanently in Tallahassee beginning in 1824, acted as ex officio superintendent throughout the existence of the superintendency. The principal Indian tribe in Florida was the Seminole.
A subagent for Indians in Florida, appointed on 21 March 1821, reported to the newly appointed provisional governor, Andrew Jackson. In September of the same year, a temporary agent was appointed to handle Indian affairs during the absence of the governor, and the subagent was made accountable to him. In 1822, an agent and a subagent were authorized to serve under the governor. In 1826, an additional subagent was appointed for the Indians on the Apalachicola River. With the contemplated removal of the Indians from Florida, the superintendency and the subagencies were abolished on 30 June 1834. In 1835, control of Indians in Florida was entrusted to the army. However, there were some Bureau of Indian Affairs officials on the Apalachicola River until 1839, and in 1849, there was a short-lived subagency for the Seminoles still in Florida.