Future rates of global groundwater depletion will depend on the economic and environmental viability of extracting water from increasingly stressed aquifers. Here we analyze global groundwater depletion by considering these factors explicitly. Global gridded groundwater availability and extraction cost data are aggregated to produce nonrenewable resource supply curves for 235 major river basins and geopolitical regions. These resources are then exposed to dynamically generated demands for water in a fully coupled, multisectoral, global simulation. As groundwater head levels drop, imposing greater capital and operating costs to bring water to the surface, modeled water use sectors are able to deploy a range of supply‐ and demand‐driven adaptive responses. Results demonstrate large sensitivity in global groundwater depletion rates to adjustments in resource exploitability. Extraction costs moderate demands for nonrenewable water substantially, resulting in the onset of a decline in global groundwater depletion rates within the twenty‐first century. New groundwater depletion hot spots may emerge as crop producers abandon overexploited basins and expand croplands in regions with cheaper, more plentiful water resources.