This study is mainly based on a wide Very High Resolution Seismic (VHRS) survey that utilized an ad hoc technique designed for investigations in very shallow waters (about 1 m depth). This method allowed the acquisition of excellent images of the subsurface down to 15–20 m b.s.l. with a resolution of about 10 cm. Buried geomorphological features, such as fluvial channel-levee systems and tidal channels, were imaged for the first time in the shallows and provided new insight into the Holocene evolution of the southern lagoon basin. Furthermore, the new seismic data were used to reconstruct the morphostratigraphic framework of the Venice Lagoon. We provide an Upper Quaternary morphostratigraphic model of the Venice Lagoon and present some evidence of radical changes resulting from human-induced river diversion in the sedimentary regime and in the morphological setting of the southern basin that has occurred over the last millennium.