The indigenous people of the Everglades region arrived in the Florida peninsula of what is now the United States approximately 14,000 to 15,000 years ago, probably following large game. The Paleo-Indians found an arid landscape that supported plants and animals adapted to prairie and xeric scrub conditions. Large animals became extinct in Florida around 11,000 years ago.

The Indigenous peoples of Florida lived in what is now known as Florida for more than 12,000 years before the time of first contact with Europeans. However, the indigenous Floridians living east of the Apalachicola River had largely died out by the early 18th century. Some Apalachees migrated to Louisiana, where their descendants now live; some were taken to Cuba and Mexico by the Spanish in the 18th century, and a few may have been absorbed into the Seminole and Miccosukee tribes.