The world's river system has more than 50,000 dams and reservoirs that offer valuable services to maximize the benefits of surface water resources (ICOLD, 2020). These benefits include flood control, hydropower generation, navigation, and recreational uses (Gao et al., 2012;A. Getirana et al., 2020;Passaia et al., 2020). Largely mandated by the Flood Control Act of 1936, the United States Army Corps of Engineers (USACE) has been building and managing numerous dams and reservoirs. Many of these reservoirs were built to attenuate flood events, thereby lowering peak flows and limiting flood inundation extents in the downstream watersheds (Turner et al., 2020). In the Mississippi River Basin (MRB) (covering 40% of the contiguous Abstract Despite the recent developments in continental-scale streamflow and flood inundation modeling frameworks, effects of time-specific and spatially explicit storage-release dynamics of numerous dams and reservoirs remain underexplored. This paper fills this knowledge gap by directly inserting operational daily flow release data at 175 dam locations into a streamflow simulation of ∼1.2 million river reaches in the Mississippi River Basin (MRB), and therefore quantifying the effect of these regulations on streamflow and flood inundation extents. Using a streamflow routing model called the Routing Application for Parallel computatIon of Discharge (RAPID) and flood inundation mapping model called AutoRoute, two simulation scenarios were constructed respectively including and excluding the daily flow releases from those dams and reservoirs for a 10-year period (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014). Flood inundation maps were simulated for peak flow conditions at a ∼10-m hyper spatial resolution. Kling-Gupta efficiency (KGE) values show that streamflow model performance considerably improved when reservoirs were included in the modeled system, varying from 2% in the eastern region to 380% in the drier western region. Despite small variation of streamflow model improvement with reservoir release inclusion in the eastern region of the basin, the flow model was able to better capture observed peak flows. For a 1% change in streamflow, we observe a 0.8% change in estimated flood inundation. Comparisons to three observed flood events in the MRB demonstrate that the flood inundation estimates improve when percent change in streamflow is relatively high. Overall, inclusion of reservoir release resulted in substantial improvement in continentalscale streamflow and flood inundation mapping.Plain Language Summary Dams and reservoirs are important structures that alter the flow of rivers to provide important services such as flood reduction, hydropower generation, and water storage for irrigation and recreation. We can use computer modeling to simulate the flow of rivers and the operation of dams. Most of the time, researchers approximate the operation of dams using various assumptions. However, we do not fully understand how much the real-life operation of reservoirs impacts rive...