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Before the colonization of the region by Spain, Lafayette and its vicinity were inhabited by the Saclan tribe of the indigenous Bay Miwok. Ohlone also populated some of the areas along Lafayette Creek. The indigenous inhabitants’ first contact with Europeans was in the late 18th century with the founding of Catholic missions in the region. These initial contacts developed into conflict, with years of armed struggle, including a battle on what is currently Lafayette soil in 1797 between the Saclan and the Spanish, and eventually resulting in the subjugation of the native population.

Most of what is currently Lafayette was given as a Mexican land grant, Rancho Acalanes to Candelario Valencia in 1834. The name Acalanes seems to have come from the name of a native village in the area, Ahala-n.

American settlement started with the arrival of Elam Brown from St. Joseph, Missouri, in 1846. He purchased Rancho Acalanes in 1848. The settlement continued to steadily grow due to its proximity to San Francisco; starting with Brown’s group of 18 settlers, by the census in 1852, 76 people were listed as living in the area. Brown founded a mill in 1853.