The first Spaniards to set foot in the region were soldiers under the command of Captain Pedro Almíndez Chirino in 1530, who reported that the area was largely uninhabited.

The Tlaxcaltecs, who had allied themselves with the Spanish in the conquest of Tenochtitlan were to serve as models of civility and of sedentary agricultural life for the still indominitable Chichimecs of the region.

On August 21, 1591, Captain Miguel Caldera, mayor of the village of Jerez and the Valley of Tlaltenango, gave the necessary land to establish a settlement.

Military governors during this period included Simon de Herrera Leiba and Pablo Enrique Yriarte Lanumbe.

These military governments were charged with all civil and criminal proceedings in the region under their rule, known as Las Fronteras de Colotlán, which in addition to Colotlan, included the provinces of Nayarit and Bolaños.

A small village in the municipality, called Agua Gorda, is the birthplace of Victoriano Huerta Márquez, President of Mexico from 1913 to 1914.

Victoriano Huerta is one of the few Presidents of Mexico who were originally from the state of Jalisco (with Valentín Gómez Farías who served as acting president twice) The area surrounding Colotlan was one of the principal battlegrounds of the Cristero Rebellion which lasted from 1927 to 1929, where pro-Catholic forces rebelled against the liberal and secularizing decrees instituted by Plutarco Elías Calles, which included suspension of worship, execution of non-compliant clergy, bans on clergy wearing clerical garb in public and on criticizing the government.

The parish priest of Totatiche, Cristóbal Magallanes Jara, who was canonized by Pope John Paul II in 1992, was executed by the Mexican government by firing squad in Colotlán on May 25, 1927 as a consequence of the Cristero conflict.

[21][22] The flag of Colotlán consists of a red rectangle with a ratio of four to seven; in the center it bears the Municipal Coat of arms in gold, placed in such a way that it occupies three-quarters of the width.