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River floods are one of the most devastating extreme hydrological events, with oftentimes remarkably negative effects for human society and the environment. Economic losses and social consequences, in terms of affected people and human fatalities, are increasing worldwide due to climate change and urbanization processes. Long-term dynamics of flood risk are intimately driven by the temporal evolution of hazard, exposure and vulnerability. Although needed for effective flood risk management, a comprehensive long-term analysis of all these components is not straightforward, mostly due to a lack of hydrological data, exposure information, and large computational resources required for 2-D flood model simulations at adequately high resolution over large spatial scales. This study tries to overcome these limitations and attempts to investigate the dynamics of different flood risk components in the Murray-Darling basin (MDB, Australia) in the period 1973–2014. To this aim, the LISFLOOD-FP model, i.e., a large-scale 2-D hydrodynamic model, and satellite-derived built-up data are employed. Results show that the maximum extension of flooded areas decreases in time, without revealing any significant geographical transfer of inundated areas across the study period. Despite this, a remarkable increment of built-up areas characterizes MDB, with larger annual increments across not-flooded locations compared to flooded areas. When combining flood hazard and exposure, we find that the overall extension of areas exposed to high flood risk more than doubled within the study period, thus highlighting the need for improving flood risk awareness and flood mitigation strategies in the near future.