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The Misión San Francisco de Asís, the sixth founded by Spanish missionaries in Alta California, was founded on 10/09/1776, dedicated to the founder of the Franciscan Order, Francis of Assisi, (née Giovanni Francesco di Bernardone, [1181 or 1182-1126]). A creek located nearby to the mission was known as "Arroyo de los Dolores," giving the church the informal name "Mission Dolores."

Pope Pius XII issued a decree naming Mission Dolores a "basilica" in 1952, the only one in the Western US at the time. This point is confusing, as the large church next door was also known popularly as a basilica.

Clapboard siding was applied to the exterior of the adobe church during the last quarter of the nineteenth century. The siding was meant to protect the adobe from rain and other natural forces of decay. The San Francisco Roman Catholic Archdiocese contracted with architect Willis Polk (1867-1924) to renovate Mission Dolores in 1917.