Prior to its foundation by Grand Master Claude de la Sengle in 1554, the land on which Senglea was built was mainly used by hunters. This explains the presence of the earliest known church built there, that dedicated to St Julian, the patron saint of hunters.
It was first erected in 1311, then rebuilt in 1539 by the Portuguese knight Fra Diego Perez de Malfreire, and finally built on the design of Lorenzo Gafà, which was completed in 1712. In 1575, before the building of the parish church proper, this church became the vice-parish of Vittoriosa.
Foremost among the churches in Senglea is its parish church, which was completed in 1581, and declared a parish prior to March 11 of that same year. Following its consecration on October 20, 1743, by Bishop Alpheran de Bussan, Pope Pius VI issued the bull for the erection of the collegiate on May 21, 1786. It was elevated to the status of a minor basilica by Pope Benedict XV on January 3, 1921.
After its reconstruction following the destruction of World War II, it was consecrated anew by Archbishop Michael Gonzi on August 24, 1957.