In that very early year of the missions, the later more favorable routing of the Camino Real, more closely aligning with the course of the Salinas River, had not yet been discovered or established.

[12] Father Junipero Serra claimed the site on July 14, 1771, and dedicated the Mission to Saint Anthony of Padua.

In 1805, the native people at the mission, mostly Northern Salinan (Antoniano) but also some Yokuts and Esselen,[13] had increased to 1,300.

[13] In 1894, roof tiles were salvaged from the property and installed on the Southern Pacific Railroad depot located in Burlingame, California, one of the first permanent structures constructed in the Mission Revival Style.

The first attempt to rebuild the Mission came in 1903 when Andrew Garriga, the pastor of the King City and Gonzales parish, and the California Historical Landmarks League began holding outings at San Antonio.

[10] Under the leadership of the Diocese of Monterey, Mission San Antonio de Padua transformed into a Catholic parish which also hosts group gatherings, gift shops and a museum with picnic grounds.

The mission is surrounded by the Fort Hunter Liggett Military Reservation, which was acquired by the U.S. Army from the Hearst family during World War II to train troops.