It was consecrated on 9 June 1727 by Bishop Melchiore Alphera in the presence of Grand Master de Vilhena and various other knights and dignitaries including the fort's commander Gio Alessio Margon.

These were later merged into a single confraternity of St Anne, and it continued to use the chapel until 1775, when it was closed to the public after the Rising of the Priests.

[1] The piazza of Fort Manoel, including the chapel and the Vilhena statue, was the subject of the earliest known photographs of Malta which were taken in 1840 by Horace Vernet while he was quarantined at the nearby Lazzaretto.

It is documented that the photographs were taken in the presence of a group of guests including Governor Henry Bouverie, but today the photos themselves seem to be lost.

[5] The building remained in ruins until it was reconstructed between 2007 and 2009[3] as part of a restoration project of the entire fort undertaken by MIDI plc.

[4] It has a classical façade with a central main doorway, four giant Ionic pilasters and two niches which formerly contained statues of saints Anthony of Padua and John the Baptist.