Accurate and timely estimates of groundwater storage changes are critical to the sustainable management of aquifers worldwide, but are hindered by the lack of in-situ groundwater measurements in most regions. Hydrologic remote sensing measurements provide a potential pathway to quantify groundwater storage changes by closing the water balance, but the degree to which remote sensing data can accurately estimate groundwater storage changes is unclear. In this study, we quantified groundwater storage changes in California’s Central Valley at two spatial scales for the period 2002 through 2020 using remote sensing data and an ensemble water balance method. To evaluate performance, we compared estimates of groundwater storage changes to three independent estimates- GRACE satellite data, groundwater wells and a groundwater flow model. Results suggest evapotranspiration has the highest uncertainty among water balance components, while precipitation has the lowest. We found that remote sensing-based groundwater storage estimates correlated well with independent estimates; annual trends during droughts fall within 15% of trends calculated using wells and groundwater models within the Central Valley. Remote sensing-based estimates also reliably estimated the long-term trend, seasonality, and rate of groundwater depletion during major drought events. Additionally, our study suggests that the proposed method estimate changes in groundwater at sub-annual latencies, which is not currently possible using other methods. The findings have implications for improving the understanding of aquifer dynamics and can inform regional water managers about the status of groundwater systems during droughts.