The chapel of the University was built in 1498 by the renowned architect of the Valencian Gothic period Pere Compte. It was completely refurbished in 1736 by Miguel Martínez in a Southern Baroque classicist variant.

It has a single vaulted nave in five bays, segmented by Corinthian pilasters with a series of arches between the columns. The presbytery is covered with a graceful oval dome whose keystone holds the coat of arms of Valencia, as the city promoted its foundation. At the foot there is a high choir that occupies the first section.

The high altar is a beautiful Baroque work in golden wood that frames the original Renaissance table of 'Nuestra Señora de la Sapiencia' (Our Lady of Wisdom), patron saint of the University, painted in 1516 by Nicolás Falcó, and surrounded by other Baroque paintings attributed to Evaristo Muñoz (1631 - 1737). Several oil paintings from the 17th and 18th centuries hang from the walls, depicting the judgment of Solomon, the revenge of Tomyris, and several saints who were linked to the Valencian academic institution A painting of the Immaculate Conception as a child is shown under the choir's vault.

Since its foundation, the Chapel has been the great assembly hall of the University, hosting not only religious services but also professor examinations, defense of theses, the conferring of academic degrees and the ‘Sabatines’, scholastic discussions between professors and students that could be witnessed by any citizen.
The chapel was completely restored between 1985 and 1990 and is often used for cultural activities: recitals, lectures and concerts.