The Royal and Pontifical University of Mexico was founded on 21 September 1551 by Royal Decree signed by Charles I of Spain, in Valladolid, Spain. It is generally considered the first university founded in North America and second in the Americas (preceded by the National University of San Marcos in Lima, Peru, chartered on May 12 of the same year).
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After the Mexican War of Independence it was renamed University of Mexico. It was closed during the years 1833, 1857, 1861 and 1865; the main reason being that it was not well regarded by the liberals, who called it an example of cultural lag.
During the Second Mexican Empire, the University was reopened by Maximilian I of Mexico and, after the victory by the liberals in 1867, closed for good. Scattered institutions, mainly civil colleges founded by the liberals and religious establishments outside Mexico City, continued without interruption.
Traditionally, the National Autonomous University of Mexico and the Pontifical University of Mexico are considered its institutional heirs.