[2][3] At the time of contact with Europeans, there were two major chiefdoms among the Mocama, the Saturiwa and the Tacatacuru, each of which evidently had authority over multiple villages.

The Mocama Province was severely depopulated in the 17th century by infectious disease and warfare with other Indian tribes and the English colonies to the north.

[9][10] Around AD 1000 peoples of the area were engaged in long-distance trading with Mississippian culture centers, including Cahokia (in present-day Illinois) and Macon, Georgia.

Some scholars, including Jerald T. Milanich and Edgar H. Sturtevant, consider the dialect known as Agua Salada, spoken in an unspecified stretch of the Florida coast south of the Mocama Province, to be identical.

[13] The French Huguenot explorers, who first arrived in Florida in 1562, recorded two major chiefdoms in the Mocama region at that time, the Saturiwa and the Tacatacuru.

[15][16] Due to severe population losses from infectious disease and warfare with northern Indian tribes and the English from South Carolina, the Mocama polity disintegrated in the 17th century.

Between 1675 and 1680, the Westo tribe, backed by the English colonies of South Carolina and Virginia, along with attacks by English-supported pirates, destroyed the Spanish mission system in Mocama.

By 1733, the Mocama and Guale chiefdoms had become too depopulated and helpless to resist James Oglethorpe's founding of the English colony of Georgia.