Water resources in the Taihu basin, China, are not only facing the effects of a changing climate but also consequences of an intensive urbanization process with the abandonment of rural activities and the resulting changes in land use/land-cover. In the present work, the impact of climate change and urbanization on hydrological processes was assessed using an integrated modeling system, coupling the distributed hydrological model variable infiltration capacity and the hydraulic model ISIS, while future climate scenarios were projected using the regional climate model providing regional climate for impact studies. Results show a significant increasing trend of impervious surface area, while other types of land cover exhibit decreasing trends in 2021–2050. Furthermore, mean annual runoff under different future climate scenarios will increase, especially during flood seasons, consistent with the changes in precipitation and evapotranspiration for both spatial and temporal distribution. Maximum and mean flood water levels under two future scenarios will be higher than levels under the baseline scenario (1961–1990), and the return periods of storms resulting in the same flood water level will decrease significantly in comparison to the baseline scenario, implying more frequent occurrence of extreme floods in future. These results are significant to future flood control efforts and waterlog drainage planning in the Taihu basin.