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Widespread episodes of recent forest die-off have been tied to the occurrence of anomalously warm droughts, although the underlying mechanisms remain inadequately understood. California's 2012-2015 drought, with exceptionally low precipitation and warmth, and widespread conifer death, provides an opportunity to explore the chain of events leading to forest die-off. Here, we present the spatial and temporal patterns of die-off and moisture deficit during California's drought, based on field and remote sensing observations. We found that die-off was closely tied to multi-year deep-rooting-zone drying, and that this relationship provides a framework with which to diagnose and predict mortality. Marked tree death in an intensively studied Sierra Nevada forest followed a four-year moisture overdraft, with cumulative 2012-2015 evapotranspiration exceeding precipitation by similar to 1,500 mm, and subsurface moisture exhaustion to 5-15-m depth. Observations across the entire Sierra Nevada further linked tree death to deep drying, with die-off and moisture overdraft covarying across latitude and elevation. Unusually dense vegetation and warm temperatures accelerated southern Sierran evapotranspiration in 2012-2015, intensifying overdraft and compounding die-off by an estimated 55%. Climate change is expected to further amplify evapotranspiration and moisture overdraft during drought, potentially increasing Sierran tree death during drought by similar to 15-20% degrees C-1.