Climate change and over-exploitation are imposing unprecedented threats to groundwater resources. Globally, groundwater reserves have depleted to the extent that well yield has decreased, pumping costs have risen, and land has irreversibly subsided. In Malawi, groundwater quantity is a national problem, specifically in Mzimba district due to severe droughts. In this study, the spatial and temporal trends of groundwater depletion were assessed using Gravity Recovery and Climate Experiment (GRACE) data and Land Surface Models (LSMs) from Global Land Data Assimilation System (GLDAS) and Global Surface Water Explorer (GSWE). The results show the following: 1. Groundwater storage is depleting at an average rate of -1.0 ± 0.06 cm yr^-1 (0.1043 km³yr^-1) in the study area with high rate of up to -1.2 cm yr^-1 (0.12516 km³ yr^-1) in the western side and as low as –0.4 cm yr^-1 (0.04172 km³ yr^-1) in the eastern part. 2. Groundwater storage increases from -13 cm in November up to 15 cm between May and April. 3. Drought is the primary cause of such depletion trends with correlation between active evapotranspiration and groundwater depletion and between downward surface shortwave radiation and groundwater depletion, at -0.577 and -0.678. respectively. The results from this study reveal the need for the scientific community and the general public to consider groundwater recharge strategies specifically by mitigating climate change to reduce prolonged droughts. This study suggests the need to establish a stand-alone groundwater assessment and monitoring authority for enhanced conservation efforts for the water resources in the country.