The Juan Bautista de Anza National Historic Trail is a 1,210 mile United States national historic trail that runs from Nogales, Arizona, on the U.S.-Mexico border, to San Francisco, California. The Trail commemorates the 1775-1776 route that Spanish commander Juan Bautista de Anza took to build a presidio and mission near San Francisco Bay.

On January 7, 1781 Father Francisco Garcés established Mission San Pedro y San Pablo de Bicuñer and a nearby pueblo was to protect the Anza Trail where it forded the Colorado River.

The settlements were inadequately supported, and Spanish colonists seized the best lands, destroyed the Indians' crops, and generally ignored the rights of the local natives. In retaliation, the Quechan (Yuma) Indians and their allies attacked and destroyed the installation between July 17 and July 19, 1781.

The natives' victory closed this crossing and seriously crippled future communications between Alta California and Mexico.

Along the Trail route, visitors can experience the varied landscapes similar to those the expedition saw; learn the stories of the expedition, its members, and descendants; better understand the Native American role in the expedition and the diversity of their cultures; and appreciate the extent of the effects of Spanish colonial settlement of Arizona and California.

The Trail was designated a National Historic Trail in 1990 and a National Millennium Trail in 1999. In 2005, Caltrans began posting signs on roads that overlap with the trail route, so that California drivers can now follow the trail.
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