The Valletta Campus, originally built as a Jesuit College, began construction in 1595 under Grand Master Martino Garzes. Located between St. Paul, St. Christopher, Merchants, and Archbishop Streets, the building features Renaissance architecture with a central courtyard. The Jesuit church, part of the complex, was built between 1592 and 1609. Initially plain, the facade was redesigned in the Baroque style around 1647 by architect Francesco Buonamici.

The interior boasts an ornate ceiling, a historic staircase, and portrait-lined corridors. Some current offices were once Jesuit priests’ cells. The building suffered major damage in a 1634 explosion and the 1693 earthquake, leading to various reconstructions. Notable additions included a sundial (1695) and a courtyard clock, both with Latin inscriptions.

After the Jesuits were expelled in 1768, the Order of St. John took over, maintaining education. In 1769, a formal University was established, re-inaugurated in 1779. During French rule (1798–1800), the building became the École Centrale, with scientific and educational functions. The British later restored the University and added a Doric-style entrance in 1824. The building was used for various purposes, including a WWII air raid center and offices such as the Anglo-Maltese Library and Heritage Malta.

Today, it hosts several institutions, including the CEU, RIDT, Conflict Resolution Centre, and the International Institute for Justice and the Rule of Law.