Upon the arrival of the knights of St. John in Malta in 1530, after having abandoned Rhodes some years earlier, Birgu was chosen as the seat of the Order. Here they established their Conventual church for their worship, the auberges for their residence, and the arsenal for the construction and maintenance of their fleet. As a result of general reconstruction taking place, Birgu was at the time referred to as "Citta Nuova", the New City. During the great siege of 1565, when Malta faced the might of the Ottoman Empire, the city played a decisive role. For its contribution towards the final victory, Grand Master La Valette renamed it "Civitas Victoriosa" which name in the Italian form, it still bears.

The motto assigned on this occasion was "Victricem palmam fero" (I bear the palms of Victory), while on the Main Gate leading to the city, a Latin quotation from the Bible was inscribed: "Obumbrasti Super caput meum in die belli - Psalm 139". (Thou hast overshadowed my head in the time of war). This was to serve as a reminder of the courage and faith displayed by the inhabitants during the Turkish Invasion.