In 1680, the Pueblo Revolt resulted in the destruction of all three missions, greatly limiting Spanish influence in the region.
In the spring of 1687, the Jesuit missionary Eusebio Francisco Kino lived and worked with the Native Americans in the area called the Pimería Alta, or "Upper Pima Country," which presently includes the Mexican state of Sonora and the southern portion of Arizona.
Following the expulsion of the Jesuits in 1767, the Franciscans from the college of Santa Cruz in Querétaro took over responsibility in the Pimería Alta missions.
However, following a Quechan raid in 1781 that destroyed two mission near present-day Yuma, the two regions remained isolated.
Following the Mexican War of Independence and the expulsion of all Spanish-born priests from the region in 1828, the remaining missions were gradually abandoned.