Its site is near the present-day city of Santa Margarita, in San Luis Obispo County, central California.

The asistencia compound was located north of the mission and of Cuesta Grade, in the Santa Lucia Mountains, on a site Padre Junípero Serra had previously chosen in 1772.

When the French privateer Hipólito Bouchard raided coastal colonial Alta California settlements in November 1818, many local residents sought refuge at this inland site.

Estrada sold Rancho Santa Margarita in 1861 to Mary and Martin Murphy Jr., who had come to Alta California with the Stephens-Townsend-Murphy Party in 1844.

Murphy erected a barn over the adobe and stone Santa Margarita de Cortona Asistencia to shield it from the elements.