Urbanization and especially increases in impervious areas, in combination with the installation of wastewater treatment infrastructure, can impact the runoff from a catchment and river flows in a significant way. These effects were studied for the Grote Nete catchment in Belgium based on a combination of empirical and model-based approaches. Effective impervious area, combined with the extent of the wastewater collection regions, was considered as an indicator for urbanization pressure. It was found that wastewater collection regions ranging outside the boundaries of the natural catchment boundaries caused changes in upstream catchment area between −16 and +3%, and upstream impervious areas between −99 and +64%. These changes lead to important intercatchment water transfers. Simulations with a physically based and spatially distributed hydrological catchment model revealed not only significant impacts of effective impervious area on seasonal runoff volumes but also low and peak river flows. Our results show the importance, as well as the difficulty, of explicitly accounting for these artificial pressures and processes in the hydrological modeling of urbanized catchments.