The present-day site of Santa Cruz was the location of Spanish settlement beginning in 1791, including Mission Santa Cruz and the pueblo of Branciforte. These settlements were part of the northern expansion of the Spanish Mexican government, and resulted in the literal and cultural genocide of the native inhabitants, the Awaswas/Amah Mutsun people.
The City of Santa Cruz was incorporated in 1866 and chartered in April 1876. Important early industries included lumber, gunpowder, lime and agriculture. Late in the 19th century, Santa Cruz established itself as a beach resort community.
Mission Santa Cruz was a site of indigenous struggle, and October 12, 1812, Father Andrés Quintana was strangled to death by mission neophytes, angry over his use of a metal-tipped whip in the punishment of laborers.