Mission San Antonio de Padua was founded on July 14, 1771, the third mission founded in California by Father Junipero Serra. The mission is named for Saint Anthony of Padua. Father Serra left Father Miguel Pieras and Father Buenaventura Sitjar behind to continue the buildings. The building of the church did not actually begin until 1810. By that time, there were 178 Indians living at the mission. By 1805, the number had increased to 1,300, but in 1834, after the secularization laws went into effect, the total number of Indians at the mission was only 150.

No town grew up around the mission, as many did at other missions. Today the nearest city is King City, nearly 29 miles (47 km) away. Jolon, a small town, is 6 miles (10 km) from the mission.

In 1845, Mexican Governor Pio Pico declared mission buildings for sale, but no one bid for Mission San Antonio. After nearly 30 years, the mission was returned to the Catholic Church. The first attempt at rebuilding the mission came in 1903, when the California Landmark League rebuilt the church's walls. In 1928, Franciscan Friars held services at San Antonio de Padua. It took nearly 50 years to completely restore the mission. In the 1940s, The Hearst Foundation gave the church $50,000 for repairs.

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. Additional land was acquired from the Army in 1950 to increase the mission area to over 85 acres (340,000 m²). This fort is still actively training troops today.

See also: California mission