The territories of the present state of Michoacan de Ocampo were occupied by diverse pre-Spaniard cultures, such as the Nahuas, the Otomies, the Matlazincas and the Tecos; however, the most important group was that of the Purepecha, a sedentary culture that practiced agriculture, was ruled by a priest called the Cazonci or "sun god", and that had full control of the economy and the warfare in the region.

Cristobal de Olid was the first Spanish colonizer to make contact with the Purepecha culture in 1522, and via friendly means he obtained the natives acknowledgement of king Charles V, even if the Cazonzi was allowed to continue as the leader of the community. Two years later Nuño de Guzman ignored such agreements and in the year 1530 had the acting Cazonzi killed. The obvious response from the outraged native population was a challenge for the missionaries from the Franciscan and Agustinian orders, especially for the distinguished lawyer Vasco deQuiroga, who contributed greatly in the process of recovering the natives trust. His efforts on behalf of the indigenous population were rewarded by his appointment as bishop in the year 1538.

During the three centuries that the Spanish colony lasted, the missionaries dedicated their time and effort to the construction of convents, schools and orphanages.

This period in the history of the western state also witnessed the rising of the mining industry in the regions of Angangueo, Tlalpujahua, Inguaran and Real Espiritu Santo, and the establishment of large Spanish Haciendas and the resulting exploitation and abusing of the indigenous population.

Michoacan is cradle to the struggle for independence, as the first conspiracy in the nation took place in 1809 in the city by then called Valladolid. Following the death of priest Hidalgo, the rebel fight was focused on the state and in the year 1811 Ignacio Lopez Rayon formed the "First National Governmental Congress" in Zitacuaro. And it was in the locality of Apatzingan that the priest and leader from Michoacan Jose Maria Morelos gave birth to the Mexican nation as he read his work "Feelings of the Nation". Other distinguished members of the rebel forces original from the state were Josefa Ortiz de Dominguez, Ignacio Lopez Rayon, Pascual Ortiz Rubio, Agustin de Iturbide and Francisco Lopez Rayon

At the Union Congress that took place in 1824, the creation of the free and sovereign state of Michoacan was declared. Then, during the fight between liberals and conservatives in the middle of the XIX century, the acting state governor Melchor Ocampo stood out as a great leader. This determined liberalist brought radical reform and change to the region until his death, for which he was honored as the state name became Michoacan de Ocampo.

During the French invasion of Mexico, the state authorities rebelled against the new Empire, which resulted in the invasion of the capital by the army of the European nation. Celebrated members of the state that struggled against yet another enemy in this period were General Regules, Manuel Garcia Pueblito and Vicente Rivapalacio. On the other hand, several Mexican Presidents were state citizens, such as Agustin de Iturdibe (1822-1823); Anastasio Bustamente (1830-1832),(1837-1839),(1839-1841); Pascual Ortiz Rubio (1930-1932); and Lazaro Cardenas (1936-1940).