According to some scholars, Pietradefusi lies on the site of the ancient Fusolae, a town cited by Livy as an allied of Hannibal during the Punic Wars, and which was later destroyed by the Romans.
The origins of the town are medieval (cited first from 1298) and it was fiefdom of many noble families such as the De Souzi, the De Tocco and the Acquaviva, but was also governed a long time by the Santa Casa dell'Annunziata of Naples. The Jesuits remember the town because one of their generals Claudio of Aragona, was born here in the times of Francesco Borgia.