To bridge the gap between 1D and 2D hydraulic models for regional scale assessment and global river routing models, we coupled the CaMa-Flood (Catchment-based Macro-scale Floodplain) model and the regional hydrological model SWIM (Soil and Water Integrated Model) as a tool for large-scale flood risk assessments. As a proof-of-concept study, we tested the coupled models in a meso-scale catchment in Germany. The Mulde River has a catchment area of ca. 6,171 km2 and is a sub-catchment of the Elbe River. The modified CaMa-Flood model routes the sub-basin-based daily runoff generated by SWIM along the river network and estimates the river discharge as well as flood inundation areas. The results show that the CaMa-Flood hydrodynamic algorithm can reproduce the daily discharges from 1991 to 2003 well. It outperforms the Muskingum flow routing method (the default routing method in the SWIM) for the 2002 extreme flood event. The simulated flood inundation area in August 2002 is comparable with the observations along the main river. However, problems may occur in upstream areas. The results presented here show the potential of the coupled models for flood risk assessments along large rivers.