The urban development of Rome (Italy) has been intertwined with the dynamics of the Tiber River since its foundation. In this review paper, we analyse more than 2500 years of flood history and urban development to untangle the dynamics of flood risk and assess the resulting socio-hydrological phenomena. Until the 1800s, urban dwellers living in the riparian areas of the Tiber River were accustomed to frequent flooding. From the 1900s, the construction of flood walls reshaped the co-evolution of hydrological, economic, political, technological, and social processes. As a result, while the probability of flooding is currently very low, its potential adverse consequences would be catastrophic. From the analysis of the long-term feedback between urban development of Rome and flood events from ancient times to present days, it emerges the crucial need for an effective flood risk mitigation strategy that combines structural and non-structural measures. In particular, heightened flood risk awareness and preparedness to cope with rare but potentially devastating events is key to alleviate flood risk.