The cathedral church is the mother church of all the churches of Malta. It is the seat of the archbishop of the whole diocese, from where he teaches, governs, and unites all the Catholics on the island. This cathedral bears the title of Metropolitan since the bishop of Malta was raised to the dignity of metropolitan archbishop and head of the ecclesiastical province of Malta and Gozo in 1944.

Since Norman times, the cathedral has been the see of the bishop of Malta, although the bishops themselves did not always reside in Malta. The succession, since the coming of the knights of the Order of St John in 1530, has been regular. Baldassare Cagliares (1615-33) was the only Maltese native to become the bishop of Malta during the knights stay, but all bishops after 1807 have been Maltese. Since the beginning of the nineteenth century and following the French occupation, the cathedral chapter started to fulfil its duties both in the cathedral in Mdina and in the co-cathedral of St Johns in Valletta, the former conventual church of the Order of St John.