Guale was a historic Native American chiefdom of Mississippian culture peoples located along the coast of present-day Georgia and the Sea Islands. Spanish Florida established its Roman Catholic missionary system in the chiefdom in the late 16th century.

The Mississippian culture was a Native American civilization that flourished in what is now the Midwestern, Eastern, and Southeastern United States from approximately 800 to 1600, varying regionally. It was known for building large, earthen platform mounds, and often other shaped mounds as well. It was composed of a series of urban settlements and satellite villages linked together by loose trading networks. The largest city was Cahokia, believed to be a major religious center located in what is present-day southern Illinois.