The Mixtón War was fought from 1540 until 1542 between the Caxcanes and other semi-nomadic Indigenous people of the area of north western Mexico against Spanish invaders, including their Aztec and Tlaxcalan allies. The war was named after Mixtón, a hill in the southern part of Zacatecas state in Mexico which served as an Indigenous stronghold.
Although other indigenous groups also fought against the Spanish in the Mixtón War, the Caxcanes were the "heart and soul" of the resistance.  The Caxcanes lived in the northern part of the present-day Mexican state of Jalisco, in southern Zacatecas, and Aguascalientes. 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. However, the Caxcanes seem to have been sedentary, depending upon agriculture for their livelihood and living in permanent towns and settlements. They were, perhaps, the most northerly of the agricultural, town-and-city dwelling peoples of interior Mexico.  The Caxcanes are believed to have spoken a Uto-Aztecan language. Other Native Americans participating in the revolt were the Zacatecos from the state of the same name.
The first contact of the Caxcan and other indigenous peoples of the northwestern Mexico with the Spanish, was in 1529 when Nuño Beltrán de Guzmán set forth from Mexico City with 300-400 Spaniards and 5,000 to 8,000 Azteca and Tlaxcalan allies on a march through Nayarit, Jalisco, Durango, Sinaloa and Zacatecas.  Over a six-year period Guzmán, who was brutal even by the standards of the day, killed, tortured, and enslaved thousands of Indians. Guzmán’s policy was to "terrorize the natives with often unprovoked killing, torture, and enslavement".  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 Indians into servitude through the encomienda system.
In Spring 1540, the Caxcanes and their allies struck back, emboldened perhaps by the fact that Governor Francisco Vásquez de Coronado had taken more than 1,600 Spaniards and Amerindian allies from the region northward with him on his expedition to what would become the United States’ Southwest.  The province was thus bereft of many of its most competent soldiers. The spark that set off the war was apparently the arrest of 18 rebellious Indian leaders and the hanging of nine of them in mid 1540. Later in the same year the Indians rose up to kill, roast, and eat the encomendero Juan de Arze.  Spanish authorities also became aware that the Indians were participating in "devilish" dances. After killing two Catholic priests, many Indians fled the encomiendas and took refuge in the mountains, especially on the hill fortress of Mixtón. Acting Governor Cristobal de Oñate led a Spanish and Indian force to quell the rebellion. The Caxcanes killed a delegation of one priest and ten Spanish soldiers. Oñate attempted to storm Mixtón, but the Indians on the summit repelled his attack.  Oñate then requested reinforcements from the capital, Mexico City. 
The Viceroy Antonio de Mendoza called upon the experienced conquistador Pedro de Alvarado to assist in putting down the revolt. Alvarado declined to await reinforcements and attacked Mixton in June 1541 with four hundred Spaniards and an unknown number of Indian allies.  He was met there by an estimated 15,000 Indians under Tenamaztle and Don Diego, a Zacateco Indian. The first attack of the Spanish was repulsed with ten Spaniards and many Indian allies killed. Subsequent attacks by Alvarado were also unsuccessful and on June 24 he was crushed when a horse fell on him. He subsequently died on July 4. 
Emboldened, the Indians attacked the city of Guadalajara in September but were repulsed.  The Indian army retired to Nochistlán and other strongpoints. The Spanish authorities were now thoroughly alarmed and feared that the revolt would spread. They assembled a force of 450 Spaniards and 30 to 60 thousand Aztec, Tlaxcalan and other Indians and under Viceroy Antonio de Mendoza invaded the land of the Caxcanes.  With his overwhelming force, Mendoza reduced the Indian strongholds one-by-one in a war of no quarter. On November 9, 1541, he captured the city of Nochistlan and Tenamaztle, but the Indian leader later escaped.  Tenamaztle would remain at large as a guerilla until 1550. In early 1542 the stronghold of Mixtón fell to the Spaniards and the rebellion was over. The aftermath of the Indian’s defeat was that "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."  By the viceroy's order men, women and children were seized and executed, some by cannon fire, some torn apart by dogs, and others stabbed. The reports of the excessive violence against civilian Indians caused the Council of the Indies to undertake a secret investigation into the conduct of the viceroy. 
As one authority said, the success of Cortés in defeating the Aztecs in only two years "created an illusion of European superiority over the Indian as a warrior." 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." 
Victory in the Mixtón War enabled the Spanish to control the region in which Guadalajara, Jalisco, Mexico’s second largest city, was located. It also opened up Spanish access to the deserts of the north in which Spanish explorers would search for and find rich silver deposits. 
After their defeat the Caxcanes were absorbed into Spanish society and lost their identity as a distinct people. They would later serve as auxiliaries to Spanish soldiers in their continued advance northward.  Spanish expansion after the Mixtón War would lead to the longer and even more bloody Chichimeca war (1550–1590). The Spanish were forced to change their policy from one of forcibly subjugating the Indians to accommodation and gradual absorption, a process taking centuries.
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- Philip Wayne Powell, quoted in " The Indigenous People of Zacatecas" by John P. Schmal, accessed Dec 23, 2010
- ^ Ewing, Russell C.; Edward Holland Spicer (1966). Russell C. Ewing. ed. Six faces of Mexico: history, people, geography, government, economy, literature & art (2 ed.). Tucson: U of AZ Press, 1966. p. 126. Retrieved August 2009. "The Spaniards did not break through into the Chichimeca country until 1541 when several groups of Chichimeca Indians were defeated in the Mixtón War"
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