The formal indigenous foundation of the town precisely coincides with the establishment of a peace treaty between tarascos (Spanish soldiers) and natives, which occurred ten years before the arrival of the conqueror Hernán Cortés. A census taken in 1580 noted 30 integrated families.
The town was conquered by
Alonso de Avalos, who nevertheless recognized the chieftainship of the original inhabitants. In 1522, Cortés dispatched one of his generals, Cristóbal de Olid to conquer Quitupan and surrounding areas. In 1530, Nuño Beltrán de Guzmán arrived to conduct a census of the native inhabitants and to impose a new order. The Evangelization of Quitupan was led by the Franciscans – in 1530, Friar Martin de Jesus began to preach, joined in 1532 by Friars Juan de Padilla and Miguel de Bologna. Viceroy Antonio de Mendoza then visited the area, under his appointment by King Charles I of Spain to pacify the various indigenous people of New Spain and to unify the territory, which was partially divided among competing conquistadors.
During the second half of the century, the region was beset by various armed confrontations between conservatives and liberals. Other historical landmarks include the Franciscan Intervention, the revolution of 1920 and the Guerra Cristera. On October 28, 1870 Quitupan was official recognized as a municipality of the state of Jalisco. Its first president was
Francisco Lorenzo Gonzalez.