The volume of groundwater stored in the subsurface in the United States decreased by almost 1000 km3 during 1900–2008. The aquifer systems with the three largest volumes of storage depletion include the High Plains aquifer, the Mississippi Embayment section of the Gulf Coastal Plain aquifer system, and the Central Valley of California. Depletion rates accelerated during 1945–1960, averaging 13.6 km3/year during the last half of the century, and after 2000 increased again to about 24 km3/year. Depletion intensity is a new parameter, introduced here, to provide a more consistent basis for comparing storage depletion problems among various aquifers by factoring in time and areal extent of the aquifer. During 2001–2008, the Central Valley of California had the largest depletion intensity. Groundwater depletion in the United States can explain 1.4% of observed sea-level rise during the 108-year study period and 2.1% during 2001–2008. Groundwater depletion must be confronted on local and regional scales to help reduce demand (primarily in irrigated agriculture) and/or increase supply.