It was first destroyed in 1597 during the Native American uprising known as Juanillo's Revolt, which led to the martyrdom of five Fransicans.
Although the Guale Indians had had regular contact with the Franciscans since 1573, the mission was not founded, according to Lanning, until 1595 by the Spanish friar Pedro Ruiz, but more recent scholarship indicates that Friar Pedro Corpa was the founder of the mission, having arrived at the village of Tolomato in 1587, accompanied by Governor Hugo de Avendaño .
The Indians attacked and burned the missions and churches in the area, but the revolt ended when an expedition led by the chieftain Asao, an ally of the Spanish, assaulted Juanillo's camp, killing him with 24 of his main supporters.
[1] The mission was not reestablished until 1605, when it was rebuilt in the Native American village of Espogache under the direction of Friar Diego Delgado.
In the mid-1620s, some of the Tolomato people who had survived the revolt of 1597 against the Spanish missions settled at Guana, three leagues north of St. Augustine, where the Spanish authorities created a new Tolomato mission intended to be a way station for a ferry service to San Juan del Puerto.