The San Juan Capistrano was founded on July 10, 1716 by Franciscan missionary Fray Isidro Felix de Espinosa during the Domingo Ramon Expedition that began in Texas in February 1716. The mission was originally named San José de los Nazonis Mission in 1716, and located in territory controlled by the Nazoni and Nadaco tribes. The mission was briefly abandoned in 1719 due to the threat of a French invasion, but was re-established at the same site by the Marques de Aguayo and Father Espinosa. San Juan Capistrano Mission was renamed on March 5, 1731, when it was relocated to the site of present San Antonio twelve miles from the Alamo. It did not make as much progress as did the other San Antonio missions because of its exposure to frequent Indian attacks and the fact that lands allotted to the mission were not sufficient for its horses and cattle and the raising of the required crops. In 1762, at least 203 Native Americans resided at San Juan Capistrano, which owned 1,000 cattle, 3,500 sheep and goats, and a horse herd of 100. Construction of a separate church was begun, but it was never completed, and services had to be held in a large room in the monastery. The buildings of the mission standing today have no sculpturing, but the walls are thick and the rooms commodious. Most of the original square remains within the walls, offering an authentic picture of the mission plan. San Juan Capistrano was transferred from the College of Santa Cruz de Querétaro to the care of the College of Nuestra Señora de Guadalupe de Zacatecas in March 1773. By the late 18th century the native population in the region declined and all renovation and construction halted in 1786. The twenty-six parcels of land associated with the Mission San Juan Capistrano were distributed on June 5, 1794, and the mission secularized on July 14, 1794. The mission was essentially abandoned from 1820 to 1840, but Reverend John M. Odin initated a revival of the Catholic institutions of Texas.
By the early 1900s regular worship was briefly restored at San Juan Capistrano under the direction of Father Francis Bouchu. From 1907 to 1908 the mission was abandoned again, until the Missionary Sons of the Immaculate Heart of Mary began reconstruction of the chapel. In 1934, as part of a public-works project, some of the Indian quarters and the unfinished church foundations were unearthed. During the 1960s the chapel, priests' quarters, and other structures were rebuilt. The mission complex was added to the National Register of Historic Places in 1972, and on February 20, 1983, a unique cooperative agreement between the United States Department of the Interior and the Archbishop of the Roman Catholic Archdiocese of San Antonio. A second agreement with the Texas Parks and Wildlife Department and the United States Department of the Interior that grouped four San Antonio missions (Purisíma Concepción, San José, San Juan Capistrano, and San Francisco de La Espada) as a National Historic Park operated, preserved, restored, maintained, and interpreted by the National Park Service as part of San Antonio Missions National Historical Park. A third agreement between the United State Department of the Interior and the San Antonio Conservation Society in consultation with the San Antonio Conservation Society Foundation provided services such as site management and interpretation.