Father Eusebio Kino, a Jesuit of Italian descent, founded the mission in 1692. It was named for Francis Xavier. The first church was built about two miles from today's site, and construction began on April 28, 1700. An Apache raid in 1770 destroyed the earlier church.
The present church was built between 1783 and 1797, which makes it the oldest European structure in Arizona. The O'odham people provided the labor.
The mission sits on the San Xavier Indian Reservation, in a settlement of the Sobaipuri O'odham. It is a pilgrimage site, with thousands visiting every year on foot and on horseback, and about 200,000 visitors a year in all.