AbstractLarge‐scale floodplains are important features of the African continent. Regular inundation provides the means to support large populations but can also present problems such as access to health facilities and water body formation that sustain malaria vectors. Modeling of these floodplains is therefore important, but complex. In this research, we develop, calibrate, and validate a hydrodynamic model of the Barotse Floodplain, of the Upper Zambezi, Zambia. The floodplain has seen recent infrastructure developments including the restoration of the canal network and construction of a cross floodplain causeway. In order to create a robust model, a multiobjective calibration uses a time slice approach based on available Landsat satellite image overpasses. An emulator‐based sensitivity analysis indicates the significance of hydrological processes in the model. Model evaluation is undertaken for two events in the gauge record (2009 and 2018), of similar magnitude that occur before and after modifications to the floodplain. Results indicate a complex impact of infrastructure development on the hydrodynamics of the floodplain, with a higher peak flow, but with a redistribution of water throughout the floodplain. Deeper flooding is observed in some areas while others experience lower water levels. The sensitivity results also reflect a change in processes, where floodplain flows dominate the 2009 event, whilst channel process dominate the 2018 event. Overall, we show that relatively modest modifications to the floodplain have impacted flood water levels, which in turn will influence access route availability and alter malaria transmission rates.