Tumacacori National Historical Park today preserves and protects San Cayetano de Calabazas, Los Santos Angeles de Guevavi and San Jose de Tumacacori, the ruins of three Spanish colonial missions in southern Arizona. Originally, more than 20 missions were established in the Pimeria Alta ("Place of the Upper Pimas") by Father Eusebio Franciso Kino and other Jesuits but these 3 are among the last remaining identifiable ruins.

The mission at San Jose de Tumacacori was first established in January, 1691, at the town of Tumacacori. Today, the National Historical Park is on 310 acres centered around the old mission structure and is open to the public through the Tumacacori Visitor Center.

The very next day in January, 1691, Father Kino established the mission at Los Santos Angeles de Guevavi. The mission at San Cayetano de Calabazas wasn't established until November of 1756 by Jesuit Father Francisco Pauer. While Tumacacori is open to the public daily, these other two sites can only be visited as part of a reservations-required ranger-guided tour on selected Wednesdays in the fall and winter months.

The conversion of the local O'odham Indians was going well from the first establishment of the missions until the discovery of large silver nuggets south of Tumacacori in 1736 brought in a large influx of miners and prospectors. The resulting disturbance to the people and the countryside led to the Pima Revolt of 1751. Throw in a few outbreaks of plague and other diseases, coupled with regular raids by the Apaches and the missions suffered greatly. 1767 saw the expulsion of the Jesuits but the Franciscans arrived in 1768 and started to put things back together again. However, the Apaches made heavy attacks in 1769, 1770 and 1771, finally forcing the Franciscans to hole up in Tumacacori with the Spanish military garrison nearby at the Presidio of Tubac, essentially abandoning missionary work in the outlying areas completely in 1775. From that point on, all the other mission structures have been decaying and returning back into the ground from which the adobe structures originally arose.

The mission church at Tumacacori was protected in 1937 by the construction of surrounding walls and a visitor center. Nearly everything except the roof and the floor are of original O'odham Indian construction from more than 200 years ago.