Completed by 1445 the Church of the Annunciation was handed over to the Domencian Friars on the 12th October 1529. These had arrived at Vittoriosa on the 4th February 1528.

During the Order’s stay in Vittoriosa (1532-72) the Church served as a Parish Church for the local population and was returned to the Parish Priest on the 8th November 1530 before being again given to the Friars on the 25th May 1531. However, in 1543 it was agreed that the Bishop had the ownership of the Church while the Friars were to enjoy its possession. The Parish Priest returned to the Church of St Lawrence when the latter was finally relinquished by the Knights.

The Church of the Annunciation was enlarged by 1578 and rebuilt between 1638 and 1657 with modifications being made over the years. It was extensively damaged in 1856 when the Convent could only carry out essential repairs. In 1864 the friars enlisted hundreds of masons, carpenters and voluntary workers to embellish the Church, which was fitted with new bells in 1880.

The Domenican Friars worked closely with the Inquisition since its establishment in 1561 – when the functions of Bishop and Inquisitor were combined – and many Domenican Friars served the Tribunal of the Holy Office. The Inquisition’s trials were held in secret although sentences were pronounced during impressive and well-attended ceremonies that were sometimes held in the Church of the Annunciation. It was in this Church that Pope Alexander VII celebrated his first High Mass in 1635, when he was an Inquisitor in Malta.

During the 1600s the Convent became a centre of learning – holding courses in philosophy and theology, both for friars as well as for secular clerics. The Centre of Learning at the Annunciation Priory was accredited the status of Stadium with the faculty to award academic degrees. This status was raised in 1866 to Studium Generale, and this prevailed up until 1872 when the courses were suspended. In 1886 this centre was transferred from Birgu to the Domenican Priory in Rabat as the latter was considered to be more accessible for the secular clergy.

During the First World War, the Church of the Annunciation became the Centre of Church Services for Maltese and British Roman Catholic servicemen stationed in Cottonera. The Vittoriosa Domenicans also had three Chaplains in the Armed Forces.

During World War II, the fate of the Domenican Friars in Vittoriosa was different. On the 19th January 1941 the church was totally destroyed, suffering extensive and irreparable damage, as well as the loss of various works of art. In 1942 the friars had to take up residence at the Inquisitor’s Palace and attend to the high number of casualties that resulted from the War.

The Church of the Annunciation was rebuilt and opened for worship in 1960.