Coarse temporal (i.e., annual) and spatial (i.e., watershed) scales camouflage water stress associated with withdrawals from surface water and groundwater sources. To address this curse of scale, we developed a framework to characterize water stress at different time scales and at fine spatial scales that have not been explored before. Our framework incorporates surface water-groundwater interactions by accounting for spatially cumulative consumptive and nonconsumptive use impacts and associated changes in flow due to depletion and return flow along stream networks. We apply the framework using a rich data set of water withdrawals from more than 6800 principal facilities (i.e., withdrawal capacity >380?000 L/day) across the U.S. Great Lakes Basin. Results underscore the importance of spatiotemporal scale and return flows when characterizing water stress. Although the majority of catchments in this water-rich region do not experience large stress, a number of small headwater catchments with sensitive streams are vulnerable to flow depletion caused by surface water and shallow groundwater withdrawals, especially in a high-withdrawal, low-flow month (e.g., August). The return flow from deep groundwater withdrawals compensates for the streamflow depletion to the extent that excess flow is likely in many catchments. The improved ability to pinpoint the imbalance between natural water supply and withdrawals based on stream-specific ecological water stress thresholds facilitates protecting fragile aquatic ecosystems in vulnerable catchments.