In 1256 the king of Sicily Manfredi of Hohenstaufen, founded the town of Manfredonia for the purpose of transferring there the population of Siponto, which, after the earthquake that destroyed it, lived in an impoverished area made unhealthy when it was turned into marshes. In 1264 the town and the castle were inaugurated by Manfredi himself, the new town obtained the status of a free trade zone and its population grew rapidly.
The Angevins completed construction of the castle with ramparts, walls and a moat; Carlo I confirmed the privileges that Manfredi gave to the town and in 1274 the Duomo was finished. In 1300 the town was on the way to becoming one of the most important trading centres of the Capitanata.