In view of the lack of ecotoxicological data for most antibiotics in China's water environment, national-scale ecological risk assessment of antibiotics remains impossible. This study determined the exposure index values for antibiotic products in the National Medical Products Administration based on quantity and average daily dose data for all antibiotics in the market alongside exposure modeling. The risk scores were calculated using data on the ecotoxicological effects of the antibiotics, and the species sensitivity distributions (SSD) method and apical effects. Priorities for control were identified based on the findings. Approximately 105 antibiotics were screened, and 53 were identified as candidate drugs with high national usage. Twenty antibiotics were identified for priority risk evaluation using a joint probabilistic model, with clarithromycin, ciprofloxacin, amoxicillin, cefaclor, and oxyfloxacin highlighted as presenting a high ecological risk. This study provides a scientific basis for the quantitative assessment of antibiotic risk prevention and control in China's aquatic environment.