The Venice Lagoon is characterized by a remarkable vertical and lateral variability of deposits, mainly produced by delta, tidal channels and sand bar migration. High resolution seismic surveys and coring analysis, carried out in the frame of the Co.Ri.La. research line 3.16, produced new insight in the evolution of the Venice Lagoon through the Holocene. Based on the new data, it has been possible, for the first time, to image and map the three main phases that characterized the formation and the evolution of the lagoon. Initially, the marine ingression, between 10,000 and 6,000 years B.P., produced the submersion by the Adriatic Sea of the Pleistocene alluvial plain. During this phase, longshore drift triggered the formation of the Venice palaeo lagoon. Then, the following sea level highstand recorded the predominance of sediment supply from rivers and the progressive advance of the coastline toward the sea. Finally, the more recent phase was characterized by the predominance of erosion and sediment exportation from the lagoon, as the consequence of human interventions on river mouths and inlets since historical time. These distinct phases are associated to sedimentary deposits with different geotechnical, sedimentological and geochemical characteristics, which play different roles in the erodibility of the sea floor and in the hydrogeological regime. In this paper we present the main results from the surveys carried between 2003 and 2006 in the southern portion of the lagoon, where the Holocene deposits reaches their maximum thickness.