The Romans founded settlements in the Venetian territory (the first was in Aquileia in 181 b.C.) and gave ample autonomy to their local communities. An essential tool for Roman penetration was the construction of the complex road system which allowed for the direct military control and the capillary diffusion of culture of the new rulers. The apex of the financial and cultural vitality took place during the 1st century b.C.. In the 3rd century, the region was affected by the general political crisis of the empire which led to the abandonment of many centres. The subsequent occupation between the 4th and 5th century had the features and prosperity of the preceding centuries. Shortly after, came the fall of the Empire and a direct consequence was the absence of a political and administrative power which would impose and organise the protection and safeguarding of the major riverbanks and draining canals; this led to the collapse of the financial system. Subsequently, the valley areas were flooded and swamped and the number of forest and wood areas increased.
After the Romans, the Byzantine resumed the maintenance work and hydraulic works along the canals; however, the arrival of the Longobards in the 6th century led to a new period of decay and the Delta returned to its natural configuration. Very little remains of the medieval fortifications when the early Estensi, Venetians, Scaglieri and Ferraresi fought for the land of the Delta.
Between the 9th and 10th century, the swamps of the Delta were, for commercial reasons, a theatre of battles between the cities of Comacchio and Venice. The Most Serene Republic won in 883 and 932 with the deportation of the survivors and the burning of Comacchio. In the two centuries that followed, the Benedictine monks of Pomposa set the law of the Delta after breaking free from the exarchate of Ravenna.
After the route of Ficarolo in 1152, the Estense dynasty managed to expand as far as the Delta, fighting against the Most Serene Republic in the Salt War (1482-1484). After the fall of the Este dynasty, the lands were passed on to the Papal State. The noble Venetians invested large capital in cultivating the land and, with the Po being diverted in 1604, they redirected the course of the river towards the South out of fear that, over time, it would submerge the Venetian lagoon. The so-called Taglio di Porto Viro (lit. the Cut of Porto Viro), redesigned the configuration of the Delta, transforming it into what it is today.
In the 16th and 17th century, the rural palazzos, villas and courts peaked in the 1700s. In 1708, several events took place: the Austrian invasion of the Delta, the siege of Ferrara and the occupation of Comacchio, which remained under Austrian ruling until 1725.