Water quality is under threat due to the presence of pathogenic and antibiotic-resistant bacteria. Escherichia coli (E. coli) serves as an indicator of faecal contamination and the potential presence of other harmful pathogens. Understanding E. coli concentrations helps in assessing the overall health risks associated with waterborne diseases and developing effective water management strategies. Therefore, we developed the first large-scale model, GloWPa-Ecoli C1 to simulate E. coli loads and concentrations in rivers and apply this model to China. The model provides the first comprehensive overview of microbial water quality across China's rivers. The model simulates E. coli concentrations in 2020 to range from 10−1.2 to 106.3 CFU/L, with 45.6 %–78.1 % of rivers exhibiting poor microbial water quality. Major hotspots of E. coli pollution are Haihe, Huaihe and Pearl River Basins. Direct discharge of human faecal waste contributes 80.2 % of the total E. coli load, while directly discharged livestock waste accounts for 13.1 %. To mitigate E. coli pollution in rivers in China, we recommend increasing human faecal waste collection rates, expanding wastewater treatment plant (WWTP) coverage, phasing out primary treatment WWTPs and eliminating direct livestock faecal waste discharge, particularly from smallholder farms. The study underscores the urgent need to improve microbial water quality in China's rivers. The findings provide actionable insights to inform policy development aimed at safeguarding water quality and public health. Furthermore, the modelling approach is applicable to other regions and microorganisms, offering a foundation for developing models to address antibiotic-resistant bacteria and other emerging water quality challenges.@en