The Native American tribes that originally inhabited the Coastal Plain were Seminole, Choctaw, and Powhatan.

The Coastal Plains were once home to the Seminole, Choctaw, and Powhatan tribes, all of whom added to the area's diverse cultural heritage. The Seminole, who live mostly in Florida, are renowned for their rich traditions and unusual resistance to attempts at eviction. The Choctaw, who live in parts of Louisiana and Mississippi, are closely linked to the land and its natural resources. An important part of early colonial history was played by the Powhatan, a confederation of tribes in Virginia. These tribes are essential to the Coastal Plains' legacy and ecological knowledge of the region because of their long-standing customs and histories.