Today the mission grounds function as a museum; the church is a chapel of ease of the Archdiocese of Los Angeles.

In 1769, the Spanish Portolà expedition – the first Europeans to see inland areas of California – traveled north through the San Fernando Valley.

Fray Juan Crespí, a Franciscan missionary travelling with the expedition, noted in his diary that the camp was "at the foot of the mountains".

The Rancho of Francisco Reyes (then the Alcalde of the Pueblo de Los Ángeles), which included the agricultural settlement of Achooykomenga worked by Ventureño Chumash, Fernandeño (Tongva), and Tataviam laborers,[11][12] was approved by the padres as a suitable site for the Mission.

After brief negotiations with the Alcalde, the land was acquired (Mission records list Reyes as godfather to the first infant baptized at San Fernando).

[15] In 1801, a 106 vara (291 feet) addition to the workshops was built and formed the south wing of the workshop courtyard; it included two granaries which became wine and aguardiente factories, two small rooms for missionaries, a weaving room, and a dormitory with a small courtyard for neophyte girls and single women.

Construction of about seventy adobe rooms for indigenous neophytes, arranged in the shape of a U, and located southwest of the convento, also began in 1804 as well as a detached tallow vat attached to the northeast corner of the quadrangle and a detached row of adobe and stone buildings running north and south to the south of the quadrangle.

This last row of buildings contained olive and grain storerooms, horse stables, a tannery and a soap factory or tallow vat called a jabonería.

The new 60 by 14 vara (165 by 38 feet) adobe and tile-roofed church was blessed on December 6, 1806, by Fray Pedro Muñoz from Mission San Miguel Arcángel.

On 21 December 1812, an earthquake hit the area which caused enough damage to necessitate the introduction of 20 new beams to support the church wall.

[17] The soldiers' unpaid wages were being supplanted by supplies and food produced in the missions which put further pressure on the neophyte indigenous labor force.

Fray Ibarra began to complain that the soldiers of his guard were causing problems by selling liquor and lending horses to the natives and in 1825, he declared that "the presidio was a curse rather than a help to the mission, that the soldiers should go to work and raise grain, and not live on the toil of the Indians, whom they robbed and deceived with talk of liberty while in reality they treated them as slaves."

[19] The Mexican government had planned to send all Spanish-born friars back to Spain; however, Fray Ibarra was allowed to stay at the mission and he continued his labors alone until the middle of 1835 when he retired to Mexico.

Fray Ordaz took charge of Mission San Gabriel, but would occasionally return to perform religious services until February 1849.

The museum became the repository for heirlooms of the Mexican church evacuated during the Cristero revolt, and also holds part of the Doheny library.

[27] The church was listed on the National Register of Historic Places in 1971, but was extensively damaged by the 1971 San Fernando earthquake, and was completely rebuilt.

Toward that end, neophytes were taught European-style farming, animal husbandry, mechanical arts and domestic crafts like tallow candle making.

It carried the following inscription (translated from Russian): "In the Year 1796, in the month of January, this bell was cast on the Island of Kodiak by the blessing of Archimandrite Joaseph, during the sojourn of Alexsandr Baranov."

It is not known how this Russian Orthodox artifact from Kodiak, Alaska made its way to a Catholic mission in Southern California.