Polignano was annexed to the Republic by Rome in 270 BC, and quickly became a commercial centre due to its large production of grain and coastal position along via Traiana, which connected Rome with Brindisi. Its geographical position assured wealth for the duration of the Emperial reign and ended only following the fall of Rome.

Polignano later became part of the Eastern Roman Empire, experiencing centuries of Longobard (VII Century), Arabic (IX Century) and Byzantine (IX-XI Century) domination.

The arrival of the Normans (XI Century) coincided with the beginning of a period of development for Apulia. This development was largely felt in Polignano due to the presence of Benedictine Monks.

Polignano fell under Swabian domination thanks to the marriage between Enrico VI and Costanza of Altavilla (1186) remaining under their direct administration until the advent of the Angioini (1266).

For a brief period, Polignano also fell under Venetian domination (1506) followed by the Reign of Italy, which was subsequently succeeded by the Spanish Crown (XVII Century).

Polignano was struck by the plague in 1690 and in the following century became Bourbon property. The City actively participated in the diffusion of Republican ideas, and the following year the city took the name of Polignano a Mare.