The area around Jerez de García Salinas was inhabited by the Zacatec and Guachichil ethnic groups prior to the arrival of the Spanish. These ethnic groups reacted in bellicose manner to the intrusion of the Spanish into their ancestral homelands. The groups, along with other Chichimeca ethic groups fought the Spanish in the Mixtón Rebellion in 1540 and the Chichimeca War beginning in 1546.



Jerez de García Salinas, was originally named Jerez de la Frontera after the town of the same name in Andalucía, Spain. The first attempt to found the town by the Spanish Crown was in 1563 to serve as a fortress on the northern frontier and guard against the incessant attacks by Chichimeca natives on the wagon trains that passed through the region en route between the mines in Zacatecas and the viceroyal capital in Guadalajara. These first attempts were unsuccessful and it was not until 1570 that the town's existence is first mentioned as being administered by the government in Tlaltenango. The following year the town was abandoned.



In 1569, the town was resettled by a group of captains waging war against the Chichimecs on the frontier. Among the founders were Pedro Carrillo Dávila, Pedro Caldera (father of Miguel Caldera), Hernán González, Cristóbal Caldera and Juan de la Torre.