Groundwater provides nearly half of irrigation water supply, and it enables resilience during drought, but in many regions of the world, it remains poorly, if at all managed. In heavily agricultural regions like California’s Central Valley, where groundwater management is being slowly implemented over a 27-year period that began in 2015, groundwater provides two–thirds or more of irrigation water during drought, which has led to falling water tables, drying wells, subsiding land, and its long-term disappearance. Here we use nearly two decades of observations from NASA’s GRACE satellite missions and show that the rate of groundwater depletion in the Central Valley has been accelerating since 2003 (1.86 km3/yr, 1961–2021; 2.41 km3/yr, 2003–2021; 8.58 km3/yr, 2019–2021), a period of megadrought in southwestern North America. Results suggest the need for expedited implementation of groundwater management in the Central Valley to ensure its availability during the increasingly intense droughts of the future.