The Mixtón War (1540–1542) was an uprisng by Caxcan people aimed at pushing the Spanish conquistadors out of northwestern Mexico and bringing the area back under indigenous control.

They are often considered part of the Chichimeca, a generic term used by the Spaniards and Aztecs for all the nomadic and semi-nomadic Native Americans living in the deserts of northern Mexico.

[5] Guzmán and his lieutenants founded towns and Spanish settlements in the region, called Nueva Galicia, including Guadalajara in or near the homeland of the Caxcanes.

But the Spaniards encountered increased resistance as they moved further from the complex hierarchical societies of Central Mexico and attempted to force natives into servitude through the encomienda system.

They assembled a force of 450 Spaniards and 30,000-60,000 Aztec, Tlaxcalan, and other natives, and under Viceroy Antonio de Mendoza invaded the land of the Caxcanes.

In the aftermath of the natives' defeat, "thousands were dragged off in chains to the mines, and many of the survivors (mostly women and children) were transported from their homelands to work on Spanish farms and haciendas.

However, the Spanish victories over the Aztecs and other complex societies "proved to be but a prelude to a far longer military struggle against the peculiar and terrifying prowess of Indian America’s more primitive warriors.

"[17] Victory in the Mixtón War enabled the Spanish to control the region in which Guadalajara, Jalisco, Mexico’s second largest city, was located.

The Spanish were forced to change their policy from one of forcibly subjugating the native population to accommodation and gradual absorption, a process taking centuries.

Annual fiestas of the Tastuanes in towns such as Moyahua de Estrada, and Apozol, Zacatecas, commemorate the Mixtón War.