The most important building of the entire university complex is the St. Ildefonsus College, the university's main building. It was built in the time of Cisneros and consisted of three interconnected courtyards: the patio Mayor de Escuelas (currently Santo Tomás de Villanueva), the patio de Continuos and the so-called patio del Colegio Nuevo. The façade of the University was built in 1537 by Rodrigo Gil de Hontañón and was finished in 1553.
The chapel of St. Ildefonsus is the work of Pedro de Gumiel, completed in 1510. It is the burial place of great figures linked to the University such as Antonio de Nebrija, Pedro de Gumiel, or the "divine" Vallés, doctor of King Philip II. It is one of the most significant examples of the "Cisneros style". In its interior the following stand out: the eight-sided polychrome wooden frame that covers the main chapel, the coffered ceiling of Mudejar carpentry that covers the area of the faithful, made by Alonso de Quevedo, and the walls, embellished with a rich and profuse plaster decoration, made in 1515. It also preserves in its interior the splendid tomb of Cisneros, one of the best examples of the classicist sculpture of the Spanish Renaissance, made in the Carrara workshop of Bartolomé Ordóñez in 1519.
The patio of Santo Tomás de Villanueva replaces the patio Mayor de Escuelas, ruined at the end of the 16th century. It was rebuilt in 1617 according to the project of Juan Gómez de Mora, chief architect of King Philip III.
The Paranymph or Scholastic Theater was the place for the imposition of degrees and where the solemn academic acts took place. It was built by Pedro de Villarroel, in 1520, under the direction of the master Gutierre de Cárdenas. The carpentry work, including its monumental wooden ceiling, was directed by Andrés de Zamora. The plasterwork tribune, with fine reliefs inspired by ornamental repertoires of Renaissance origin, is the place from which where the teachers of the university gave their teachings and where the future university doctors defended their degrees.