Freshwater supplies in most western Canadian watersheds are threatened by the warming of temperatures because it alters the snow-dominated hydrologic patterns that characterize these cold regions. In this study, we used datasets from 12 climate simulations, which are associated with seven global climate models and four future scenarios and are participating in phase 6 of the Coupled Model Intercomparison Project, to calculate and assess the historical and future temporal patterns of 13 hydroclimate indicators relevant to water resources management. We conducted linear long-term trend and change analyses on their annual time series to provide insight into the potential regional impacts of the detected changes on water availability for all users. We implemented our framework on the Alberta oil sands region in Canada to support the monitoring of environmental changes in this region, relative to the established baseline 1985–2014. Our analysis indicates a persistent increase in the occurrence of extreme hot temperatures, fewer extreme cold temperatures, and an increase in warm spells and heatwaves, while precipitation-related indices show minor changes. Consequently, deficits in regional water availability during summer and water-year periods, as depicted by the standardized precipitation evapotranspiration indices, are expected. The combined effects of the strong climate warming signals and the small increases in precipitation annual amounts generally detected in this study suggest that drier conditions may become severe and frequent in the Alberta oil sands region. The challenging climate change risks identified for this region should therefore be continuously monitored, updated, and integrated to support a sustainable management for all water users.