Spain's establishment of missions for the purpose of Christianizing the Indian population was one of the methods used in their colonization of La Florida in the sixteenth century. Initially, missions were staffed by the Jesuits. Due to the hostility of the Indians, which resulted in the murder of several of the missionaries, the Jesuits withdrew from the mission field in La Florida in 1572. Franciscan friars entered into La Florida in 1573, but at first confined their activities to the immediate vicinity of St. Augustine. By 1587, they began taking their mission to the Guale and Timucua Indians along the Atlantic coast.
The Saturiwa, a Timucua speaking tribe who lived in the Mocama Province, were allied with the French of Fort Caroline, and were thus initially hostile to the Spanish – who ousted the French colonists from the Florida coast in 1565. Huguenot leader René Goulaine de Laudonnière records that their chief, who was known as Saturiwa, had sovereignty over thirty villages and their chiefs, ten of whom were his "brothers". These villages were located around the mouth of the St. Johns River and nearby inland waterways. However, the Saturiwa soon made peace with the Spaniards, and Mission of San Juan del Puerto was founded near their main town on Fort George Island in the late 1580s. During a visit in 1606 by Bishop Altamirano, it was recorded that the mission had over 500 members, including the female Cacique Maria and five of her subordinate caciques from the area.
While working at this mission, Father Francisco Pareja prepared a Timucuan dictionary, grammar and several religious books in that language for use by the Indians. In 1612, he printed a catechism in Spanish and Timucua, the first book printed in an indigenous language of the Americas. By 1627, he had published eight other works in Spanish and Timucua, for the use of his teaching brothers; six works survive. He found that the Timucuans had a knack for languages and could be taught to read and write within six months. Since the twentieth century, his work has also been studied for insights into the ethnography of the indigenous people.
The noted botanist, writer, and explorer, John Bartram, visited Fort George Island in 1766. He inspected the site of the former Spanish mission and the huge shell middens deposited there by generations of Native Americans. He described what he saw as "several middling tumulus's or sepulchers of the Florida Indians...'Tis very demonstrable that the Spaniards had a fine settlement here, as there still remain their cedar posts on each side their fine straight avenues, pieces of hewn live-oaks, and great trees girdled round to kill them, which are now very sound, though above 60 years since they were cut. This rich island, though it appears sandy on the surface, yet hath a clay bottom, above which in some places there is a dark-coloured strata of indurated sand-rock."
The Ribault Club is a historic Colonial Revival architecture style building that is home to the Fort George Island Visitor Center. The property was added to the U.S. National Register of Historic Places on May 11, 2000 and is located on Fort George Road. It was built in 1928 for winter recreational opportunities which included golf, tennis, hunting, fishing, and yachting. Ribault Club became part of the Fort George Island Cultural State Park in 1989. Exhibits about the island and its history are located inside.