A major reconstruction to designs of Carlos de Grunenbergh took place in the 1690s, giving the fort its current appearance.

[2] The site was occupied since pre-history and a prominent place of worship in antiquity with the building of the temple of Astarte.

Large ashlar blocks and an Egyptian pink granite column at the top part of the fort still exists inside the chapel.

[4][5] A rock-cut church close to the area had already existed since Orthodox Christianity in Malta around 600 A.D. and was rebuilt with wood in around 800 A.D.[6] Its probable start as a fortification is the high/late medieval period.

In fact, in 1220 Hohenstaufen Emperor Frederick II started to appoint his own Castellani for Malta who needed a place to live and secure the interests of the crown.

[12] When the Order of Saint John arrived in Malta in 1530, they chose to settle in Birgu, when it was observed the site of Fort St Angelo was partially abandoned and in ruins.

[13] After renovation it became the seat of the Grand Master, which included the refurbishing of the Castellan's House and the Chapel of St Anne.

The Knights made this their primary fortification and substantially reinforced and remodelled it, including the cutting of the dry ditch to make it a moat and the D'Homedes Bastion built by 1536.

[1] When the French arrived in 1798, the fort had become a powerful fortification housing some 80 guns, 48 of which pointed towards the entrance of the port.

With the coming of the British to Malta the fort retained its importance as a military installation, first in use by the Army as a Wireless Station.

On 5 December 1998, a treaty was signed between Malta and the Sovereign Military Order of Malta granting the upper part of Fort St Angelo, including the Grand Master's House and the Chapel of St Anne, to the Order with limited extraterritoriality.

[22][23] On 5 March 2012, it was confirmed that the European Regional Development Fund allocated €13.4 million for the restoration, conservation and re-use of the site, allowing for the Fort to be opened as a major visitor attraction highlighting its history and roles through the ages as well as to cater for educational programs, cultural events and live historical experiences.

[26] It frequently participates in hosting events of national importance including the Commonwealth Heads of Government Meeting 2015[27] and the 2017 Maltese EU presidency.