The shipwreck of St Paul on Malta is recounted in the Acts of the Apostles, where there is also a mention of the miracles and several healings that the Apostle carried out during his stay in Malta. One person St Paul healed was Publius’ father. Publius, the then Roman prefect of Malta, is said to have been made the head of the first Maltese community. It is to him that this church is dedicated.

The Sanctuary of St Publius was added on to the Church of St Paul in 1617. This was taken care of by the knights of the Order of St John, which is very evident from the numerous eight-pointed crosses found all over the sides of the sanctuary.  The adjacent and connecting church of St Paul is the present parish church of Rabat. It is not known when a church was first erected here, but the present edifice is dated to the 17th century. The Church of St Paul was built through the generosity of the noble woman Cosmana Navarra, of which there are numerous items on exhibit at the Wignacourt Museum. These two churches share a common facade. It almost seems like the architect Francesco Buonamici tried to alleviate the rivalry between the Church and the Order by giving both entrances the same prominence. This makes most onlookers believe that there is only one Church. 

The sanctuary of St Publius is a richly decorated sacred place. The titular panting is by the renowned Italian artist, Mattia Preti, showing the Virgin and Child with St John the Baptist and Publius. The eight-pointed cross is very much in evidence as it can be seen clutched in the hand of Baby Jesus, thus inferring that the Order of St John is under divine protection. There are two lateral paintings in the main apse, one is showing St Publius preaching and the other one is showing the martyrdom of the saint. In the main aisle of the church there are four canvases which reflect the dedication and history of this sanctuary. There are paintings showing the baptism of Publius and the consecration of Publius as the bishop of Malta. The other two canvases are portraits, one is depicting Alof de Wignacourt, the French Grandmaster who worked hard to increase the devotion towards the cult of St Paul; the other portrait shows Pope Paul V, a great benefactor of the Grotto and the sanctuary.

In 1753 a small chapel was added to the right of the main altar. This is dedicated to the Blessed Sacrament. The painting here showing the Last Supper of Christ is by the Maltese artist Francesco Zahra. The side chapel is decorated with other paintings and rich stonework, typical of the 18th century baroque.