The Tigua people were forced from Isleta Pueblo after the 1680 Pueblo Revolt. In 1682 they built a permanent adobe building here, and it was dedicated that October. The mission is recognized as the oldest continuously operated parish in Texas.
A flood in 1829 washed the structure away, and the Rio Grande's new course put the site in the Republic of Texas. A remodel in 1897 added the beehive-shaped bell tower.
The 1907 fire caused huge damage and the church was rebuilt in 1908. It became a Recorded Texas Historic Landmark in 1962 and joined the National Register of Historic Places on July 31, 1972.

