This study compared numerical simulations of the hydro-morphodynamics of a stretch of the Po River (Italy) to detailed measurements of the river's morphology and water–sediment fluxes. A survey of the 8-km-long, 250-m-wide river section, previously described in former publications, was performed using two vessels. The first was equipped with a multibeam echo sounder for bathymetry and the investigation of bed forms, while the second was equipped with two acoustic Doppler current profilers (ADCPs) to map bed roughness, flow velocity, and suspended sediment fields. This paper focuses on the calibration of the shallow water numerical model MIKE21C implemented by the Danish Hydraulic Institute. Sensitivity analyses were performed to analyze the effects of bed roughness and sediment transport direction on the simulated flow field and morphology. The results fixed the predominant flow and morphology parameters in the model, and show how the velocity and sediment field maps that were derived from the ADCP recording could be used for calibration and validation of the existing software.