Geo-historical information deduced from geo-iconographical resources, derived from extensive research and the selection of cartographies and historical documents, enabled the investigation of the natural and anthropic transformations of the perifluvial area of the Po River in the Emilia-Romagna region (Italy). This territory, significant in terms of its historical, cultural, and environmental contexts, for centuries has been the scene of flood events. These have characterised the morphological and dynamic variability in the riverbed and relative floodplain. The close relationship between man and river is well documented: the interference induced by anthropic activity has alternated with the sometimes-damaging effects of river dynamics. The attention given to the fluvial region of the Po River and its main tributaries, in a peculiar lowland sector near Parma, is critical for understanding spatial–temporal changes contributing to current geo-hydrological risks. A GIS project outlined the geomorphological aspects that define the considerable variations in the course of the Po River (involving width reductions of up to 66% and length changes of up to 14%) and its confluences from the 16th to the 21st century. Knowledge of anthropic modifications is essential as a tool within land-use planning and enhancing community awareness in risk-mitigation activities and strategic management. This study highlights the importance of interdisciplinary geo-historical studies that are complementary in order to decode river dynamics in damaging flood events and latent hazards in an altered river environment.