Evaluation of hydrological response to future climate change is essential for water quality risk assessment and adaptive management implementation within a watershed context. In this study, we present a modeling framework that integrates a hydrological model with projections of General Circulation Models (GCMs). Temperature and precipitation projections of six GCMs with two downscaling methods are used to force the Soil and Water Assessment Tool (SWAT) model in the Hamilton Harbour watershed in Ontario, Canada. A flow-based weighting strategy was developed to integrate the projections of multiple GCMs based on their ability to recreate empirical flow frequency distributions in multiple monitoring sites. Our study renders support to the ability of the weighted model ensemble to draw meaningful hydrological forecasts. Nonetheless, we also note that the ensemble strategy understates the frequency and magnitude of flow extremes, and therefore the domain that is collectively delineated by individual GCMs can still provide complementary planning information. Climate change is projected to trigger a distinct increase in air temperature and precipitation during the late winter-early spring period, which in turn will likely result in an earlier snowmelt and changes in the magnitude and timing of peak flow events. Analysis of the water cycle shows that the sensitivity of the individual hydrological components to climate change may vary along the urban-to-agriculture gradient. The projected declining soil–water content in agricultural catchments highlights the likelihood of more intensified drought conditions in the croplands. Evapotranspiration rates will likely increase across the entire watershed, whereas surface runoff could be reduced but less so in urbanized locations. Overall, our findings suggest that any future planning exercise to ameliorate the prevailing water quality conditions will only be insightful if we consider the interplay between climate change and urbanization processes in the area.