At the insistence of Fray Juan de Zumarraga and of the viceroy Antonio de Mendoza, in Tlatelolco the first center of high aprenidization was founded in America, and shortly thereafter were humanistic Indians. To Santa Cruz de Tlatelolco were sent the most advanced students of the schools in monasteries.
The school was located inside the courtyard of the monastery of Santiago de Tlatelolco, first, it was a modest architecture building built by orders of Carlos V, first owner of that house, later it was rebuilt and embellished by Fray Bernardino de Sahagún. This man spoke with the Indians in Nahuatl and wrote a Spanish-Nahuatl and Latin-Nahuatl dictionary in twelve volumes.
In 1551 the permission of the foundation of the Royal and Pontifical University of Mexico was received, this university as much as other European institutions was considered canonical, which made that the permission passed by the Pope, so that the canonical foundation was authorized . The university was opened on January 25, 1553, a solemn Mass was sung in the Church of St. Paul and from there a procession of schools took off.
The first president of the University was Don Juan Manuel de Negrete and among the first professors were: Fray Alonso de Veracruz, who taught theology, Juan García in arts, Francisco Cervantes de Salazar in manual arts and Blas de Bustamante in grammar. The lessons began to be given on June 5, 1553, there were about 100 founding students.