Discharges of combined sewer system overflows (CSOs) affect water quality in drinking water sources despite increasing regulation and discharge restrictions. A hydrodynamic model was applied to simulate the transport and dispersion of fecal contaminants from CSO discharges and to quantify the impacts of climate and population changes on the water quality of the river used as a drinking water source in Quebec, Canada. The dispersion model was used to quantify Escherichia coli (E. coli) concentrations at drinking water intakes. Extreme flows during high and low water events were based on a frequency analysis in current and future climate scenarios. The increase of the number of discharges was quantified in current and future climate scenarios with regards to the frequency of overflows observed between 2009 and 2012. For future climate scenarios, effects of an increase of population were estimated according to current population growth statistics, independently of local changes in precipitation that are more difficult to predict than changes to regional scale hydrology. Under “business-as-usual” scenarios restricting increases in CSO discharge frequency, mean E. coli concentrations at downstream drinking water intakes are expected to increase by up to 87% depending on the future climate scenario and could lead to changes in drinking water treatment requirements for the worst case scenarios. The greatest uncertainties are related to future local discharge loads. Climate change adaptation with regards to drinking water quality must focus on characterizing the impacts of global change at a local scale. Source water protection planning must consider the impacts of climate and population change to avoid further degradation of water quality.