In the late 4th century A.D. the town changes deeply as a result of the destruction probably caused by the earthquake of 365 A.D. and of the transformations introduced by the administrative reform of the Empire promoted by Constantine the Great. From this moment onwards and until the 6th century A.D., the urban landscape responds to a new plan, in which is recognizable the influence of the bishop in promoting the construction of religious buildings and in encouraging the local production and trade exchanges.

Towards the end of the 4th century the episcopal basilica with the baptistery is built, then renovated and enlarged in the last years of the 5th century, when the bishop’s seat is held by Rufentius. In 501 and 502 the prelate signs the acts of the Roman synods as episcopus Egnatinae ecclesiae among the first positions on the list of bishops gathered in Rome, thus demonstrating the prestige of the diocese of Egnazia. During the rise of the bishop’s church, the imposing monument of Imperial age located south of the forum is presumably transformed into a religious building with a longitudinal plan.

Between the late 5th and the 6th centuries the southern basilica, located few metres south-east of the bishop’s building, is added to the pre-existing monuments, while the civil basilica is probably adapted for the Christian cult and a small church monumentalises the far north-west sector of the town, still dynamic and organized.

In the new private buildings, residential spaces, production areas and livestock farming areas coexist, as in the case of the district south of the via Traiana. In this area, in addition to the main production of pottery, the processing of bones and the production of lime come alongside, the latter being the true “protagonist” among the products of the town, which now sees a new flourishing of the art of building. Besides the lime workshop related to the building yard of the episcopal basilica, in the early 5th century also the thermal baths are transformed into a factory for the production of lime and bricks, while a large lime kiln erases all traces of decoration from the sanctuary by providing the construction material for the residential complex that occupies and transforms the building of worship of the acropolis.

The dynamic economy, partly thanks to the port that supplies the town with goods coming from every corner of the Mediterranean basin, ensures continuity to the market square, which experiences a new season of activity.

Towards the end of the 6th century, while the town is gradually abandoned, mainly because of the difficulty in draining the alluvial deposits, some tombs of the western necropolis start to house the remaining inhabitants. The acropolis, instead, is reorganized within a Byzantine fortification that protects the port against the threats coming from the inland. With this reorganization the settlement lives in the form of a village until the 13th century.