Although the use of the Gravity Recovery and Climate Experiment (GRACE) satellites to monitor groundwater storage changes has become commonplace, our evaluation suggests that careful processing of the GRACE data is necessary to extract a representative signal especially in regions with significant surface water storage (i.e., lakes/reservoirs). In our study, we use cautiously processed data sets, including GRACE, lake altimetry, and model soil moisture, to reduce scaling factor bias and compare GRACE‐derived groundwater storage changes to in situ groundwater observations over parts of East Africa. Over the period 2007–2010, a strong correlation between in situ groundwater storage changes and GRACE groundwater estimates (Spearman's ρ = 0.6) is found. Piecewise trend analyses for the GRACE groundwater estimates reveal significant negative storage changes that are attributed to groundwater use and climate variability. Further analysis comparing groundwater and satellite precipitation data sets permits identification of regional groundwater characterization. For example, our results identify potentially permeable and/or shallow groundwater systems underlying Tanzania and deep and/or less permeable groundwater systems underlying the Upper Nile basin. Regional groundwater behaviors in the semiarid regions of Northern Kenya are attributed to hydraulic connections to recharge zones outside the subbasin boundary. Our results prove the utility of applying GRACE in monitoring groundwater resources in hydrologically complex regions that are undersampled and where policies limit data accessibility.