He was the governor of the province of Pánuco from 1525 to 1533 and of Nueva Galicia from 1529 to 1534, and president of the first Royal Audiencia of Mexico – the high court that governed New Spain – from 1528 to 1530.

Originally a bodyguard of Charles I of Spain, he was sent to Mexico to counterbalance the influence of the leader of the Spanish conquest of the Aztec Empire, Hernán Cortés, since the King worried he was becoming too powerful.

He conducted numerous expeditions of conquest into the northwestern areas of Mexico, enslaving thousands of Indians and shipping them to the Caribbean colonies.

[2]: 59–65  For a period he and his younger brother served as one of 100 royal bodyguards of Carlos V, and he accompanied the Emperor on a trip to Flanders in 1522, and undertook sensitive diplomatic missions, including one dealing with the Bishop of Cuenca (Spain).

His appointment was opposed by the Pro-Cortés faction of the struggle for power in early colonial Mexico, who viewed him as an outsider with no military experience.

[1]: 170  But he had the support of the Council of Indies and the Spanish Crown who saw him as a counterbalance to the figure of Cortés whose aspirations to power worried the King of Spain.

In spite of his lack of success as governor, in 1529 he was appointed President of the First Audiencia, which the Council of the Indies and the Crown instated to check the ventures of industrious private individuals, such as Cortés, in New Spain.

At the time Guzmán was serving as governor of Pánuco, so Charles ordered the judges to assemble in Veracruz and from there make a joint entrance into the capital.

Most of these associates had participated in the government in the proceeding few years while Cortés was in Honduras, with a lot of in-fighting among themselves and injustices to the population, both Spanish and Indigenous.

Among his official acts was placing plaques bearing the royal coat of arms on the principal buildings of the capital, to stress that sovereignty resided in the king, not in Cortés.

This was so effective that Bishop Zumárraga felt the necessity of hiding a letter sealed in wax in a cask, to be smuggled to the Spanish authorities by a confederate sailor.

In 1530, upon Hernán Cortés' return to New Spain, Guzmán was removed from the office of President of the Audiencia and instead appointed governor of Nueva Galicia.

Then, gathering a military force of 300 to 400 discontented conquistadors and between 5,000 and 8,000 indigenous Nahua allies, Guzmán set out on December 21, 1529, to the west of Mexico City to conquer lands and peoples who until then had resisted the conquest.

The campaign started with the torture and execution of the Purépecha cazonci Tangáxuan II, a powerful indigenous ally of the Spanish Crown.

Guzmán proceeded to launch a fierce campaign into the Chichimec lands in the province that was to become known as Nueva Galicia, reaching as far as Culiacán.

[6] Typically, the conquistadors attacked an Indian village, stole the maize and other food, razed and burned the dwellings, and tortured the native leaders to gather information on what riches could be stolen there, or from nearby populations.

In 1531 (probably January), one of Guzmán's captains, Cristóbal de Oñate, founded a small town near Nochistlán to which the name "Guadalajara" was given.

Two years later Guzmán visited the city, and at the request of its inhabitants, who were fearful of Indian attacks and lacked sufficient water, he ordered it moved to Tonalá.

Later the settlers began to complain to Antonio de Mendoza, then the viceroy of New Spain, about both the repeated relocations and Guzmán's cruelty.

One nineteenth-century chronicler of the Conquest referred to Beltrán de Guzmán as "the detestable governor of Pánuco and perhaps the most depraved man ever to set foot in New Spain.

"[10] Reports of Guzmán's treatment of the Indigenous had reached Mexico City and Spain, and, at Bishop Zumárraga's request the Crown sent Diego Pérez de la Torre to investigate.

"[11] In 1558 he wrote his last will which was uncovered in 1973, it shows him as a poverty stricken noble struggling to save his heirs from his debts, having had even to pawn his heirlooms to pay for medicine.

[2]: 280–81 In posteriority and partly in his own time Nuño de Guzmán achieved a reputation as the worst villain of the conquistadors, in the words of his biographer Donald Chipman he has been depicted as the "personification of the Black Legend".

[citation needed] His biographer Santana describes his personality as characterized by "cruelty of the highest order, ambition without limit, a refined hypocrisy, great immorality, ingratitude without equal, and a fierce hatred for Cortés".