On this site stood successive buildings of the metropolitan church of St Titus Church, which from 1211 functioned as the seat of the Latin archbishopric. After the fall of the city, the last three-aisled basilica, built in 1544, underwent extensive alterations in order to be converted into a mosque dedicated to the conqueror of Candia, Fazıl Ahmed Köprülü. It became known as the Vezir Mosque (Vezir Camii).

The conversion involved squaring the ground plan and changing the orientation of the building. A three-doored, column-supported porch was created on the site of the former sanctuary apse, while the mihrab was installed on the southern side within a domed structure supported by four columns. A monumental minaret was erected on the south-west side of the mosque.

The mosque complex included a religious school, rooms for students’ accommodation, a reception hall and additional auxiliary buildings. The Ottoman traveller Evliya Çelebi notes that the mosque possessed exceptionally elaborate glasswork, a finely decorated mihrab and an ornate pulpit (minbar).

The earthquake of 1856 reduced the mosque to ruins. In 1869, the Grand Vizier Ali Pasha commissioned the Epirus-born architect Athanasios Mousis to rebuild a grand mosque, which was inaugurated in 1871. For the construction of the new eclectic building, stone and marble were reused from the Venetian monastery of St Francis Monastery, which had been demolished in 1867 and had previously housed the imperial mosque.

Above the western entrance, the new mosque bore a marble inscription designed by the renowned calligrapher Mustafa Irfani, recording the Hijri dates 1288 (1871/72), 1310 (1892/93) and 1311 (1893/94). The mosque was associated with a cemetery for the burial of prominent individuals. In the surrounding area stood the charitable fountain of Köprülü and a domed, hexagonal fountain for ritual ablutions.

After the departure of the last Muslim inhabitants of Heraklion following the compulsory population exchange between Greece and Turkey, the minaret was demolished and, in 1925, the building resumed use as an Orthodox church dedicated once again to St Titus.
In 1995, limited archaeological investigation and restoration works were carried out by the 13th Ephorate of Byzantine Antiquities. Further conservation works were undertaken in 2023 by the Directorate for the Conservation of Ancient and Modern Monuments.