This study presents an analysis of climate change impacts on a large river located in Québec (Canada) used as a drinking water source. Combined sewer overflow (CSO) effluents are the primary source of fecal contamination of the river. An analysis of river flowrates was conducted using historical data and predicted flows from a future climate scenario. A spatio-temporal analysis of water quality trends with regard to fecal contamination was performed and the effects of changing flowrates on the dilution of fecal contaminants were analyzed. Along the river, there was a significant spatial trend for increasing fecal pollution downstream of CSO outfalls. Escherichia coli concentrations (upper 95th percentile) increased linearly from 2002 to 2012 at one drinking water treatment plant intake. Two critical periods in the current climate were identified for the drinking water intakes considering both potential contaminant loads and flowrates: local spring snowmelt that precedes river peak flow and extra-tropical storm events that occur during low flows. Regionally, climate change is expected to increase the intensity of the impacts of hydrological conditions on water quality in the studied basin. Based on climate projections, it is expected that spring snowmelt will occur earlier and extreme spring flowrates will increase and low flows will generally decrease. High and low flows are major factors related to the potential degradation of water quality of the river. However, the observed degradation of water quality over the past 10 years suggests that urban development and population growth may have played a greater role than climate. However, climate change impacts will likely be observed over a longer period. Source water protection plans should consider climate change impacts on the dilution of contaminants in addition to local land uses changes in order to maintain or improve water quality.