Upgrades of wastewater treatment plant (WWTP) and full-scale application of additional advanced oxidation processes have been proven to be effective in reducing the nutrient emissions to the environment; however, the impacts of WWTP upgrades on the receiving waters with regard to the occurrence and ecological risks of pharmaceuticals are still unclear. In this study, 27 pharmaceuticals with diverse physicochemical properties were monitored in four rivers in Beijing, each of which was heavily impacted by a large-scale WWTP. Three-year sampling campaigns were conducted, covering the periods before and after the WWTP upgrades. The results show that the newly added combined treatment processes (e.g., biological filter, ultrafiltration, ozonation, and NaClO disinfection) reduced the total pharmaceutical concentrations in the effluents by 45–74%. The composition profiles reveal that the upgrades of two studied WWTPs resulted in a significant reduction of pharmaceutical concentrations in the receiving rivers, while little impacts were observed for the other rivers. The risk assessment shows that the acute toxic pressures in the studied rivers were generally low and the WWTP upgrades were conducive to reduce the risks for most of pharmaceuticals. However, erythromycin and ofloxacin still posed high risk, indicating the potential adverse effect of pharmaceuticals on aquatic environment.