The main objective of this research was to understand the effects of climate change on soil water content (SWC) across the Qu’Appelle River basin in southern Saskatchewan, Canada. The Soil and Water Assessment Tool (SWAT) and output from 11 high-resolution (0.22°) regional climate models (RCM) were used over three 30-year periods: the near future (2021–2050) and distant future (2051–2080) and the historical reference (1975–2005). The RCM data are from the CORDEX North American domain, which employs the RCP8.5 high-emission scenario. SWC was modeled at the hydrological response units (HRU) level and at daily and monthly (warm season only) intervals for 2015–2020. The model was calibrated and validated using SUFI-2 in SWAT-CUP based on observations for streamflow and SWC, including measured data and Soil Moisture Active Passive (SMAP) Level 4 for surface (up to 5 cm deep) soil moisture. Values of the Nash–Sutcliffe model efficiency (NS) ranged from 0.616 and 0.784 and the coefficient of determination (R2) was 0.8 for calibration and 0.82 for validation. Likewise, the correlation coefficients between ground measurements and SWAT were 0.698 and 0.633, respectively. Future climate forcing of the calibrated SWAT model revealed that warmer and drier growing seasons will prevail in the region. Similarly, the ensemble of all RCMs indicated that the mean temperature will increase by 2.1 °C and 3.4 °C for the middle and late periods, respectively, along with a precipitation increase of 10% and 11.2%. SWC is expected to decrease with an increase in potential evapotranspiration, despite an increase in precipitation. Likewise, the annual SWC is expected to decrease by 3.6% and 4% in the middle and late periods, respectively. The monthly SWC changes showed the highest decreases (5.4%) in April in the late period. The spatial pattern of SWC for 11 RCMs was similar such that the northwest and west of the river basin are wetter than the south and east. SWC projections suggest that southern Saskatchewan could experience significant SWC deficiencies in the summer by the end of this century.