Abstract. Increasing population, economic growth and changes in diet have dramatically increased the demand for food and water over the last decades. To meet increasing demands, irrigated agriculture has expanded into semi-arid areas with limited precipitation and surface water availability. This has greatly intensified the dependence of irrigated crops on groundwater withdrawal and caused a steady increase in groundwater withdrawal and groundwater depletion. One of the effects of groundwater pumping is the reduction in streamflow through capture of groundwater recharge, with detrimental effects on aquatic ecosystems. The degree to which groundwater withdrawal affects streamflow or groundwater storage depends on the nature of the groundwater–surface water interaction (GWSI). So far, analytical solutions that have been derived to calculate the impact of groundwater on streamflow depletion involve single wells and streams and do not allow the GWSI to shift from connected to disconnected, i.e. from a situation with two-way interaction to one with a one-way interaction between groundwater and surface water. Including this shift and also analysing the effects of many wells requires numerical groundwater models that are expensive to set up. Here, we introduce an analytical framework based on a simple lumped conceptual model that allows us to estimate to what extent groundwater withdrawal affects groundwater heads and streamflow at regional scales. It accounts for a shift in GWSI, calculates at which critical withdrawal rate such a shift is expected, and when it is likely to occur after withdrawal commences. It also provides estimates of streamflow depletion and which part of the groundwater withdrawal comes out of groundwater storage and which parts from a reduction in streamflow. After a local sensitivity analysis, the framework is combined with parameters and inputs from a global hydrological model and subsequently used to provide global maps of critical withdrawal rates and timing, the areas where current withdrawal exceeds critical limits and maps of groundwater and streamflow depletion rates that result from groundwater withdrawal. The resulting global depletion rates are compared with estimates from in situ observations and regional and global groundwater models and satellites. Pairing of the analytical framework with more complex global hydrological models presents a screening tool for fast first-order assessments of regional-scale groundwater sustainability and for supporting hydro-economic models that require simple relationships between groundwater withdrawal rates and the evolution of pumping costs and environmental externalities.