Sustainable use of groundwater is critical to China's present and future food security. Natural groundwater resources of Huang-Huai-Hai plains (HHH), the region that produces 60-80% of China's wheat (Triticum aestivum) and 35-40% of its maize (Zea mays), are being jeopardized by excessive water withdrawal. While previous studies have assessed the groundwater depletion rate in parts of this region, there is a lack of data on the rate of groundwater depletion and the corresponding change process analysis at the entire scale in the HHH. In this article, we document that the groundwater is being depleted at a mean rate of 0.46 ± 0.37 m year-1 for the shallow aquifer and 1.14 ± 0.58 m year-1 for deep aquifer. Based on the general specific yield of aquifer in the HHH, the rate of loss of total groundwater in the entire region is 8.32-10.75 km3 year-1. The severity of groundwater depletion is attributed to the long-term intensive irrigation for increasing crop yields and total biomass production in the HHH. Increasing 1 million Mg of wheat production lower the deep groundwater by 1.8 m (e.g., in Dezhou in the flood and coastal plains) and the shallow groundwater by 0.37 m (e.g., in Shijiazhuang in the piedmont plains). Thus, effective measures must be adopted to mitigate groundwater depletion for sustaining the present level of food production in the HHH.