Groundwater depletion is becoming a global threat to food security, yet the ultimate impacts of depletion on agricultural production and the efficacy of available adaptation strategies remain poorly quantified. We use high-resolution satellite and census data from India, the world's largest consumer of groundwater, to quantify the impacts of groundwater depletion on cropping intensity, a crucial driver of agricultural production. Our results suggest that, given current depletion trends, cropping intensity may decrease by 20% nationwide and by 68% in groundwater-depleted regions. Even if surface irrigation delivery is increased as a supply-side adaptation strategy, which is being widely promoted by the Indian government, cropping intensity will decrease, become more vulnerable to interannual rainfall variability, and become more spatially uneven. We find that groundwater and canal irrigation are not substitutable and that additional adaptation strategies will be necessary to maintain current levels of production in the face of groundwater depletion.