Construction of the building began in 1595, and it originally housed a Jesuit college known as the Collegium Melitense Societatis Jesu.

The precursor to the University of Malta was the Collegium Melitense Societatis Jesu, a Jesuit college which was set up on 12 November 1592.

[7][8] The building was designed by Giuseppe Valeriano[9] (later alterations were carried out by other architects, possibly including Vincenzo Casanova).

[10] Construction of the present building began on 4 September 1595 when the foundation stone was laid down by Grand Master Martin Garzez.

[6] In the early 18th century, part of the building was converted into a permanent exhibition by housing artifacts from Ciantar's antiquities collection which came from his former residence in Marsa.

However, soon after the expulsion of the Jesuits, the collection went sparse among those interested to acquire them with minimal concern over the preservation of the artifacts.

[16] The University of Malta officially came to existence on 22 November 1769, when Grand Master Manuel Pinto da Fonseca signed a decree constituting a Pubblica Università di Studi Generali.

[6] Today, the Valletta Campus houses the International Collaborative Programmes,[22] the Research Innovation & Development Trust[23] and the Conferences and Events Unit.

[29] The rear entrance which was opened in 1824 is an example of neoclassical architecture, and it consists of an archway with two Doric columns supporting a lintel, above which is a representation of the Royal coat of arms of the United Kingdom.

The design seems to have been inspired from the Hôtel d'Hallwyll [fr] by Claude Nicolas Ledoux, which was built in Paris in 1766–70.