Anthropogenic water pollution severely threatens human society worldwide, yet the water pollution induced by combined sewer overflow (CSO) remains unclear within climate change and urbanization. Hence, this study integrated the general circulation model (GCM) and shared socioeconomic pathway (SSP) projections with water quality modeling, to analyze spatiotemporal patterns and future trends of CSO-induced water pollution under changing environments. Results demonstrated that the given area (Dresden, Germany) encountered significant CSO-induced pollution, with 14,860 kg (95 % confidence interval, CI: 9,040-15,630 kg) of particulate matter (SS), organic compounds (COD, TN, TP), and pharmaceuticals (Carbamazepine, Gabapentin, Ciprofloxacin, Sulfamethoxazole) being discharged annually. Climate change and urbanization exacerbated the severity of CSO-induced pollution, causing the discharged pollutants to reach a maximum annual load of 34,900 kg (CI: 21,400-44,100 kg), with up to 82.19 % of organic compounds and 75.28 % of pharmaceuticals being discharged by the top 25 % of extreme CSOs. GIS-based spatial analysis indicated the regional heterogeneities of CSO-induced pollution, the high-frequency CSOs were predominantly located in highly-impervious areas, while the high-load discharges mainly occurred in densely-populated areas. Scenario analysis revealed stronger temporal variabilities of CSO-induced pollution in the future, with the seasonal anomalies of discharged loads ranging from -86.18 % to 76.89 %. In addition, pharmaceutical pollution exhibited significant uncertainties under changing environments, and the CI of discharged load expanded by up to 131.71 %. The methods and findings herein yielded further insights into water quality management in response to changing environments.