Franciscan missionaries established this mission in 1749 in the hope of civilizing and christianizing the Coco, Mayeye, Orcoquiza, Karankawa, and other Indian tribes. The martyrdom of Padre José Ganzabal and the circumstances connected with it caused the departure of the Indians and the friars and the removal of the mission to the San Marcos River in 1755. It was reestablished in 1762 on the Nueces River for the conversion of the Lipan Apaches under the new name Mission San Lorenzo de la Santa Cruz.