The reason for his transfer was that the Dominican Archbishop Diego de Deza wanted him as one of the first fellows (colegiales) of the newly founded College of St. Thomas Aquinas in that city.

Apart from the appointments within the Dominican Order, Montúfar served for a long time as a theological consultant of the tribunals of the Inquisition in Granada, Murcia, Toledo and Seville.

After the death of the first Archbishop of Mexico, Franciscan Don Juan de Zumárraga, Dominican friar Montúfar was named as the new archbishop by Emperor Charles V. The recommendation of Montúfar as a candidate to the Mexican see seems to have come from Luis Hurtado de Mendoza y Pacheco, 2nd Marquis of Mondejar, who at the time was President of the Council of the Indies.

In the mid-1560s, Montúfar sent a secular priest, Juan de Vivero, the chaplain for the galleon San Geronimo, to the newly conquered Philippine Islands in order to establish the structures of the Catholic Church there.

Vivero arrived in the islands in 1566, and founded the first Catholic church there, dedicated to the Immaculate Conception, later to become the cathedral of the Diocese of Manila after its establishment in 1579.

Already complaining about his advanced age and general fragility, Archbishop Montúfar wrote to the King that he wanted to convoke this assembly before his death, which he thought would come very soon.

Despite three decades of missionary work, Montúfar argued that the greater part of the indigenous population was as pagan as it had been before the conquest and that the Church lacked both order and discipline.

Even if Montúfar sometimes admitted that the mendicant missionary Franciscans, Dominicans and Augustinians had done much for the evangelization of the Indians and that he as Archbishop could do very little without them, he felt that they had gained too much power and influence.

On the other hand, Montúfar thought that he was entrusted with very little power and if the Archdiocese could be described as a patchwork of missionary parishes, known as doctrinas, most of them were outside the control of the prelate as friars administered them.

With such a deficient knowledge of the basis of the Christian doctrine and infrequent contact with the sacraments of the Church, Montúfar doubted whether many of the Indians souls would be saved.

Sometimes Montúfar asserted that ten times as many priests were needed in order to teach the Christian doctrine and administer the sacraments to the native population.

To meet the needs of the Indian ministry, Montúfar wanted to build a seminary in Mexico City, where a large number of young criollos could be educated and later serve as priests.

If there were no priests living in the village, he believed that the Indians would easily become victims of the native religious experts (hechiceros), who would lure them back to their old beliefs and ceremonies.

If the Indians were forced to pay tithes, the friars thought that they would despise the Church and its ministers and think that they were driven by greed and not by love for their souls.

In short, the friars thought that the introduction of secular priests and the imposition of tithes would rapidly destroy all that they had built up since they had arrived in New Spain.

One of the first sources of the cultus of Our Lady of Guadalupe at Tepeyac in the outskirts of the city of Mexico was a collection of testimonies against the Franciscan Minister Provincial Francisco de Bustamante, which was drawn up by Montúfar in 1556.

Many people, both Spaniards and Indians, and men and women from all social strata, traveled to Tepeyac to pay devotion to Our Lady and the image of her that had been placed there, and gave great amounts of alms.

Nevertheless, the witnesses stress specifically the piety of upper-class Spaniards who made pilgrimages to Tepeyac and entered the chapel on their bare knees.

In the document, the church building at Tepeyac is referred to as an ermita, a word signifying a chapel of ease, often to be found in rural areas or in the outskirts of a town and without resident clergy.

According to witnesses, Montúfar expressed his pleasure that many people in various parts of the world held images of the Virgin Mary in high esteem.

The following Tuesday, September 8, on the feast day of the Nativity of Mary, the Franciscan Minister Provincial, Francisco de Bustamante, preached on the Virgin in the Chapel of San José de los Naturales, commonly called the Indians' chapel, the original shrine built to honor the Virgin.

According to the testimony of Juan de Salazar, Bustamante continued, stating that he: did not know what effect the said devotion had, because it would contradict what he and other members of religious orders with much sweat had been preaching to the natives of this country.

Both Spanish colonists and Indians from the city of Mexico and its environs went there to pay devotion to Our Lady, to do penitence and to be cured from illnesses that afflicted them.