With improving healthcare and an aging population, the consumption of human pharmaceuticals in China has been increasing dramatically. Environmental risks posed by many active pharmaceutical ingredients (APIs) are still unknown. This study used a spatially explicit dilution-factor methodology to model predicted environmental concentrations (PECs) of 11 human-use APIs in surface water for a preliminary environmental risk assessment (ERA). Median PECs in surface water across China range between 0.01 and 8.0 × 103 ng/L for the different APIs, under a moderate patient use scenario. Higher environmental risks of APIs in surface water are in regions with high water stress, e.g., northern China. Levonorgestrel, estradiol, ethinyl estradiol and abiraterone acetate were predicted to potentially pose a high or moderate environmental risk in China if consumption levels reach those in Europe. Relative risks of these four APIs have the potential to be among those chemicals with the highest impact on surface water in China when compared to the risks associated with other regulated chemicals, including triclosan and some standard water quality parameters including BOD5 (5-day biological oxygen demand), COD (chemical oxygen demand), Cu, Zn, and Hg and linear alkylbenzene sulfonate. This method could support the regulation of this category of chemicals and risk mitigation strategies in China.