The city of Tallahassee is situated in an area once occupied by Native Americans. The Apalachee village of Anhaica was captured in the winter of 1538 by Hernando DeSoto; his treatment of the Apalachees was brutal. He moved on with the arrival of spring in 1539 to continue his explorations.

Throughout the 17th century, Spanish missionaries moved into the area. Their association with the Apalachee was to provide a means of food and labor for the Spanish settlement of Saint Augustine. At some point in the 18th century, the Creeks moved into the area, with them came the Muskogean word "Tallahassee", meaning old fields or old town.

During these times, there were two major cities in Florida, Pensacola and Saint Augustine. Government business was conducted in both cities, with delegates traveling to each city as required, alternating the meetings between the two cities.

Finally, in 1821, Spain ceded Florida to the United States. In 1823, Tallahassee was established as its territorial capital. It was centrally located between Pensacola and Saint Augustine. Florida would remain a U.S. territory until it achieved statehood in 1845 and Tallahassee remained its capital.