This paper presents the first application and validation of a 2D hydrodynamic model of the Amazon at a large spatial scale. The simulation results suggest that a significantly higher proportion of total flow is routed through the floodplain than previously thought. We use the hydrodynamic model LISFLOOD‐FP with topographic data from the Shuttle Radar Topography Mission to predict floodplain inundation for a 240 × 125 km section of the central Amazon floodplain in Brazil and compare our results to satellite‐derived estimates of inundation extent, existing gauged data and satellite altimetry. We find that model accuracy is good at high water (72% spatial fit; 0.99 m root mean square error in water stage heights), while accuracy drops at low water (23%; 3.17 m) due to incomplete drainage of the floodplain resulting from errors in topographic data and omission of floodplain hydrologic processes from this initial model.