Construction of the church began in April 1700, and Kino in his autobiography relates: “On the 28th we began the foundations of a very large and capacious church of San Xavier del Bac, all the many people working with much pleasure and zeal, some in digging the foundations, others in hauling many and very good stones of tezontle from a little hill about a quarter of a league away. For the mortar for these foundations it was not necessary to haul water, because by means of irrigation ditches we very easily conducted the water where we wished. And that house, with its great court and garden nearby, will be able to have throughout the year all the water it may need, running to any place or workroom one may please, and one of the greatest and best fields in all Nueva Biscaya ... on the 29th we continued laying the foundations of the church and of the house.” (Note: The site of these foundations is not where the present mission stands, but at a point some two miles north.)
Kino died in 1711 and it is uncertain how much of the building had been completed. In 1751 the generally peaceful Pimas, disturbed by the inroads being made by Spanish settlers and prospectors, revolted and plundered the mission. Some of the Indians had been obliged to work in the mines, practically as slaves for the Spanish colonists, and it is probable that others found the discipline and regular work of the padres burdensome. All Pimería was shaken by this great uprising which nearly wiped out the frontier missions.
The following year a presidio was established at the visita of Tubac, 37 miles to the south, for the protection of San Xavier, its visitas, and the villages of the Christian Indians. Missionary activities were again started and many of the Indians who had previously fled, returned.
In 1767, by Royal Order, the Jesuits were expelled from all Spanish domain. Charles III of Spain, fearing the Jesuits were too persistent in their quest of new lands, decided to replace them with the Franciscan Order. San Xavier, like most of the abandoned missions of the region, was taken over by the Franciscans in 1768. San Xavier came under the direction of Friar Francisco Garcés and before the year was out, while he lay sick at a nearby visita, the mission buildings were destroyed by Apaches.