It was a religious outpost established by Spanish Catholic Franciscans, to spread Christianity among the local Native Americans.

The San Agustin de la Isleta Mission was founded on the older pueblo, on the west bank of the Rio Grande about 13 miles (21 km) south of Albuquerque.

The Tiwa accompanied some of the Spanish colonists, moving south to El Paso, Texas to the Ysleta Mission del Sur.

San Agustin continued to operate the Pueblo of Isleta under Spanish and then Mexican rule for fifty years longer.

Anton Docher arrived from Belgium in the late 19th century and was assigned to the Pueblo of Isleta after several years in the region.

In 1923, he undertook a major remodeling of the Isleta mission, adding prominent French-style gothic spires on the adobe walls.