The Knights took over this medieval fort in 1530 and strengthened it – Fort St Angelo served as the residence of the Grand Master of the Order until 1571 and was the headquarters of la Valette during the Great Siege. In the 17th century the talented engineer Don Carlos Grunenberg added more defences. At the time of research Heritage Malta was due to open sections of the fort to the public, with hands-on interpretative exhibits and access to amazing harbour views.

The British occupied the fort from the 19th century, and from 1912 until 1979 it served as the headquarters of the Mediterranean Fleet, first as HMS Egmont and from 1933 as HMS St Angelo. The upper part of the fort, including the Grand Master's Palace and the 15th-century Chapel of St Anne, is now occupied by the modern Order of St John. The tip of the Vittoriosa peninsula has been fortified since at least the 9th century; before that it was the site of Roman and Phoenician temples.