Effective monitoring of groundwater withdrawals is necessary to help mitigate the negative impacts of aquifer depletion. In this study, we develop a holistic approach that combines water balance components with a machine learning model to estimate groundwater withdrawals. We use both multi-temporal satellite and modeled data from sensors that measure different components of the water balance at varying spatial and temporal resolutions. These remote sensing products include evapotranspiration, precipitation, and land cover. Due to the inherent complexity of integrating these data sets and subsequently relating them to groundwater withdrawals using physical models, we apply random forests- a state of the art machine learning algorithm- to overcome such limitations. Here, we predict groundwater withdrawals per unit area over a highly monitored portion of the High Plains aquifer in the central United States at 5 km resolution for the years 2002-2019. Our modeled withdrawals had high accuracy on both training and testing datasets (R≈ 0.99 and R≈ 0.93, respectively) during leave-one-out (year) cross-validation with low Mean Absolute Error (MAE) ≈ 4.26 mm and Root Mean Square Error (RMSE) ≈ 13.57 mm for the year 2014. Moreover, we found that even for the extreme drought year of 2012, we have a satisfactory test score (R≈ 0.79) with MAE ≈ 10.34 mm and RMSE ≈ 27.04 mm. Therefore, the proposed hybrid water balance and machine learning approach can be applied to similar regions for proactive water management practices.