This study analyzed the impact of socio-economic development and climate change on levels of faecal indicator bacteria in the Betna River in Bangladesh. Water samples were tested to measure E. coli and enterococci concentrations. A hydrodynamic model and microbial model were used to validate measured bacteria levels and simulate future scenarios. The models found that human waste contributed more bacteria than livestock. Future socio-economic changes like population growth and sanitation levels were found to have a greater impact on bacteria levels than climate changes like increased temperature and precipitation. Improved sanitation and wastewater treatment were recommended to reduce bacteria in the river.