On 30 December 1680, Pope Innocent xi appointed Dun Karlu Magri as Archpriest of the Matrice. One of the church’s most eminent archpriests, he soon got the bishop’s approval for the building of a new church. He set aside a special fund for the purpose, began acquiring property adjoining the new church, and engaged Lorenzo Gafà, the best architect at that time, to carry out the preliminary studies. These were concluded by 1687.
On 11 January 1693, the old church was irretrievably damaged by a severe earthquake and this hastened the project. Magri died later that same year and his successor, Dun Nikol Natal Cassia-Magri wholeheartedly proceeded with the project. On 21 September 1697, in an elaborate ceremony, he laid the foundation stone of the present Cathedral. It was at this time that the base of the Roman temple that previously rose on the site was discovered.
The orientation of the new church was in line with that of the previous one. The apse faced due east, the Orient and Jerusalem — which in Biblical imagery stands for the heavenly Jerusalem — and the principal entrance due west. So universally was this orientation carried out in ancient times, that the Gospel side came to be known as the North side, where the men assembled, and the Epistle side as the South side, where the women assembled. This strict rule was generally observed from the eleventh century up to the Renaissance, when the observance was more or less abandoned. This orientation attests to the antiquity of the former church.
Gafà had prepared a scale model of the new building, which allowed work to continue uninterrupted after his death early in 1703. The new church was officially inaugurated on the eve of the Assumption, 14 August 1711. It was dedicated by Bishop Giacomo Cañaves in a solemn, twenty-four-hour-long ceremony on 11 October 1716. Archpriest Cassia-Magri and his successors proceeded to enhance and embellish the church with works of art.
On 10 June 1798, General Bonaparte ousted the Knights from Malta, but in September the Maltese rose against the French. The Gozitan uprising was led by the Archpriest of the Matrice Saverio Cassar, who succeeded in incarcerating all the French troops on the island within Iċ-Ċittadella walls. On 28 October, the French surrendered. For nearly two years Gozo became an independent country known as La Nazione Gozitana. This came to an end on 5 September 1800, when British rule (1800–1964) was ushered in.
On 16 September 1864, Pope Pius ix established the diocese of Gozo and Comino. The Matrice was declared the Cathedral of the new diocese.
A cathedral church is one that is presided over by a bishop and in which the bishop has its cathedra or throne. The faithful of the diocese regard the church as the Mother of all churches in the diocese. The cathedral is served by a chapter or body of canons whose duty it is to chant the Divine Office daily in choir. The present Cathedral Chapter is made up of eighteen canons who have the title of Monsignors. Gozo and its Cathedral has had eight bishops since 1864.