The Spanish presence in Florida produced a network of Catholic missions that operated for a century among the Native American populations of Florida and Georgia. Extending north from St. Augustine was a series of missions to the Timucua and Guale Indians.

Missions were located on the islands of Ft. George, Amelia, Cumberland, St. Simons, and St. Catherines and at several nearby mainland sites. Another series of missions around present-day Tallahassee reinforced a settled agricultural existence among the Apalachee Indians, and near present-day Gainesville missions oriented to cattle grazing thrived. By the mid-seventeenth century, some 26,000 Christianized Indians lived in and near some three dozen missions. Archeologists have determined the locations of many of the Spanish missions, including Santa Catalina on St. Catherines Island, San Juan del Puerto on Ft. George Island, and San Luis de Talimali in present-day Tallahassee (a state historic site).

This sophisticated network, however, did not prevent raids by English colonists that eventually forced the Spanish to abandon the missions. The founding of the colony of Georgia increased tensions between the English and Spanish leading up to the Seven Years War. After losing the war, Spain surrendered Florida to Britain in 1763. Sparsely populated and insecure, Florida remained under British control during the American Revolution.

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