The church is built over the ditch of the Roman city which also included a large part of Rabat. The church is also built over the grotto where according to tradition St. Paul was kept prisoner during his three months stay in Malta in 60 A.D. In 1336 bishop Hilarius refers to the church as ecclesia Sancti Pauli de crypta , and also mentions the cemetery and the Roman ditch. Several churches have been built on the site both by the diocese and the Knights of St. John. The present church was built with funds provided by the noble woman Guzmana Navarra on plans prepared by F. Bonamico. The church was completed by Lorenzo Gafà in 1683.
The Auberge de Castille was the official seat of the knights of the Langue of Castille, León and Portugal – one of the most powerful of the Order of St. John, its Head being the Grand Chancellor. The Knights of this Langue were responsible for the defence of part of the fortifications of Valletta, known as the St Barbara Bastion. The Auberge is situated at the highest point of Valletta and originally looked out on the rolling countryside beyond, giving it a unique vantage-point unsurpassed by any other building in the city. The original Auberge was built by the renowned Maltese architect Girolamo Cassar in 1574. It was extensively re-modelled and virtually rebuilt in 1741, the present plan of the imposing structure attributed to Andrea Belli. The building was damaged during the siege of the French forces (1799–1800) as well as during the Second World War (1939–1945).