Sahagún is perhaps best known as the compiler of the Historia general de las cosas de la Nueva España—in English, General History of the Things of New Spain—(hereinafter referred to as Historia General). The most famous extant manuscript of the Historia General is the Florentine Codex. It is a codex consisting of 2,400 pages organized into twelve books, with approximately 2,500 illustrations drawn by native artists using both native and European techniques. The alphabetic text is bilingual in Spanish and Nahuatl on opposing folios, and the pictorials should be considered a third kind of text. It documents the culture, religious cosmology (worldview), ritual practices, society, economics, and history of the Aztec people, and in Book 12 gives an account of the conquest of Mexico from the Tenochtitlan-Tlatelolco point of view. In the process of putting together the Historia general, Sahagún pioneered new methods for gathering ethnographic information and validating its accuracy. The Historia general has been called "one of the most remarkable accounts of a non-Western culture ever composed," and Sahagún has been called the father of American ethnography.
Fray Bernardino was born Bernardino de Rivera (Ribera, Ribeira) 1499 in Sahagún, Spain. He attended the University of Salamanca, where he was exposed to the currents of Renaissance humanism. During this period, the university at Salamanca was strongly influenced by Erasmus, and was a center for Spanish Franciscan intellectual life. It was there that he joined the Order of Friars Minor or Franciscans. He was probably ordained around 1527. Entering the order he followed the Franciscan custom of changing his family name for the name of his birth town, becoming Bernardino de Sahagún.
Spanish conquistadores led by Hernán Cortez conquered the Aztec capital of Tenochtitlan (on the site of present-day Mexico City) in 1521, and Franciscan missionaries followed shortly thereafter in 1524. Sahagún was not in this first group of twelve friars, which arrived in New Spain in 1524. An account, in both Spanish and Nahúatl, of the disputation that these Franciscan friars held in Tenochtitlan soon after their arrival was made by Sahagún in 1564, in order to provide a model for future missionaries. Thanks to his own academic and religious reputation, Sahagún was recruited in 1529 to join the missionary effort in New Spain. He would spend the next 61 years there.
During the Age of Discovery, 1450–1700, Iberian rulers took a great interest in the missionary evangelization of indigenous peoples encountered in newly discovered lands. In Catholic Spain and Portugal, the missionary project was funded by Catholic monarchs under the patronato real issued by the Pope to ensure Catholic missionary work was part of a broader project of conquest and colonization.
The decades after the Spanish conquest witnessed a dramatic transformation of indigenous culture, a transformation with a religious dimension that contributed to the creation of Mexican culture. People from both the Spanish and indigenous cultures held a wide range of opinions and views about what was happening in this transformation.