It was built from 1532 by the great architect Antonio da Sangallo the Younger, probably with the help of his assistant Antonio Lapaco. The same Sangallo the Younger is the author of Rocca Paulina from Perugia and Fortezza da Basso from Florence. These three fortifications were the basis for the confirmation of Pope Clement VII's policy in central Italy. In fact, the Pope attempted to respond to the bag of Rome, which weakened his status and economic capacity.
On June 19, 2008, Ancona Castle became the seat of the permanent secretariat of the Ionian Adriatic Initiative, an international body coordinating the political work of Italy, Slovenia, Croatia, Montenegro, Albania, Bosnia and Herzegovina and Greece. After becoming the seat of such a body, an important restoration of the castle was carried out, which included the Guardia stronghold, but will extend to other areas.