The origins of the University of Valencia date back to the fifteenth century, when the Juries of Valencia decided to unify the different higher education centres of the city in one place. For this, the University bought the houses located in the place where its historical seat stands today, and commissioned in 1498 the famous architect Pere Compte, author of the Lonja and other important works in the Cathedral and the Generalitat, to adapt these buildings to house the Studium Generale. The statutes were drawn up in 1499 and approved by Pope Alexander VI. Ferdinand II the Catholic granted its official status as a university.

For centuries, the situation of the University remained peaceful, with periods of great splendour. Many personalities taught and learned in its classrooms: the philosopher Luis Vives, the humanists Rojas Clemente and Honorato Juan, the naturalist Cavanilles, the scientist Corachán, the mathematician Tomás Vicente Tosca, the scholars Gregorio Mayans and Francisco Perez Bayer, and the researchers Ferran and Ramón y Cajal.

The building of the University was badly damaged in the bombing of the city in 1812 by Napoleonic troops commanded by Marshal Suchet. The ensuing fire destroyed the library, the classrooms and the offices, leaving the Paranimf and the Chapel as the only remains. The laborious work to restore the building was carried out throughout the nineteenth century.
In 1844 the University lost its economic and institutional autonomy and was placed under the control of the central State. Its professors became civil servants. A Natural History Museum was established, which was destroyed by fire in 1932.

Nowadays, the academic activity of the University is developed in the faculties and schools spread over its three campuses, as well as in various research institutes located throughout the city of Valencia. The historic building houses now the Historical Library, rectories and various administrative, bureaucratic and cultural services.