Groundwater used for irrigation is critical to US agriculture and exports, but its role in non-agricultural sectors and broader US supply chains is poorly understood. This study tracks how unsustainable groundwater withdrawals and irrigation infrastructure contribute to supply chains across the US economy. Using data on crop-specific irrigation, groundwater depletion, well infrastructure, and 2012 economic data, we map virtual groundwater flows — groundwater embedded in goods and services — through economic sectors and regions. We find 68.3 km3 of irrigation groundwater was virtually transferred across supply chains, with 38.1 km3 (56%) being unsustainable. Major metropolitan areas received the largest shares of depletionary virtual groundwater. Key aquifers, including the California Central Valley, High Plains, and Mississippi Embayment, contributed 71% of all virtual groundwater flows. The government sector consumed 31% of final unsustainable virtual groundwater. Critical hotspots in the full supply chain that depend on virtual groundwater embedded in intermediary and final goods and services were identified in California, Arkansas, Louisiana, and Texas. Spatial patterns of well infrastructure closely mirrored virtual water flows. These findings improve understanding of how unsustainable groundwater use is embedded in the US economy and highlight regions and sectors most dependent on depleted water resources.