Mission San Gabriel was founded on September 8, 1771 by Father Junipero Serra. The planned site for the Mission was along the banks of the Río de los Temblores (the River of the Earthquakes—the Santa Ana River). The priests chose an alternate site on a fertile plain located directly alongside the Rio Hondo in the Whittier Narrows.

The site of the Misión Vieja (or "Old Mission") is located near the intersection of San Gabriel Boulevard and Lincoln Avenue in Montebello, California (known to the natives as Shevaanga). In 1776, a flash flood destroyed much of the crops and ruined the Mission complex, which was subsequently relocated five miles closer to the mountains in present-day San Gabriel (the native settlement of 'Iisanchanga). The Mission is the base from which the pueblo that became the city of Los Angeles was sent.

Well over 25,000 baptisms were conducted at San Gabriel between 1771 and 1834, making it the most prolific in the mission chain. In its heyday it furnished food and supplies to settlements and other missions throughout California. A majority of the Mission structures fell into ruins after it was secularized in November 1834. The once-extensive vineyards were falling to decay, with fences broken down and animals roaming freely through it.

The Mission's chapel functioned as a parish church for the City of San Gabriel from 1862 until 1908, when the Claretian Missionary Fathers came to San Gabriel and began the job of rebuilding and restoring the Mission. On October 1, 1987 the Whittier Narrows Earthquake damaged the property. A significant portion of the original complex has since been restored.

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