Natural and human-induced impacts on water resources across the globe continue to negatively impact water resources. Characterizing the hydrologic sensitivity to climatic and anthropogenic changes is problematic given the lack of monitoring networks and global-scale model uncertainties. This study presents an integrated methodology combining satellite remote sensing (e.g., GRACE, TRMM), hydrologic modeling (e.g., SWAT), and climate projections (IPCC AR5), to evaluate the impact of climatic and man-made changes on groundwater and surface water resources. The approach was carried out on two scales: regional (Morocco) and watershed (Souss Basin, Morocco) to capture the recent climatic changes in precipitation and total water storage, examine current and projected impacts on total water resources (surface and groundwater), and investigate the link between climate change and groundwater resources. Simulated (1979–2014) potential renewable groundwater resources obtained from SWAT are ~4.3 × 108 m3/yr. GRACE data (2002–2016) indicates a decline in total water storage anomaly of ~0.019m/yr., while precipitation remains relatively constant through the same time period (2002–2016), suggesting human interactions as the major underlying cause of depleting groundwater reserves. Results highlight the need for further conservation of diminishing groundwater resources and a more complete understanding of the links and impacts of climate change on groundwater resources.