Parsimonious groundwater modeling provides insight into hydrogeologic functioning of the Nubian Aquifer System (NAS), the world’s largest non-renewable groundwater system (belonging to Chad, Egypt, Libya, and Sudan). Classical groundwater-resource issues exist (magnitude and lateral extent of drawdown near pumping centers) with joint international management questions regarding transboundary drawdown. Much of NAS is thick, containing a large volume of high-quality groundwater, but receives insignificant recharge, so water-resource availability is time-limited. Informative aquifer data are lacking regarding large-scale response, providing only local-scale information near pumps. Proxy data provide primary underpinning for understanding regional response: Holocene water-table decline from the previous pluvial period, after thousands of years, results in current oasis/sabkha locations where the water table still intersects the ground. Depletion is found to be controlled by two regional parameters, hydraulic diffusivity and vertical anisotropy of permeability. Secondary data that provide insight are drawdowns near pumps and isotope-groundwater ages (million-year-old groundwaters in Egypt). The resultant strong simply structured three-dimensional model representation captures the essence of NAS regional groundwater-flow behavior. Model forecasts inform resource management that transboundary drawdown will likely be minimal—a nonissue—whereas drawdown within pumping centers may become excessive, requiring alternative extraction schemes; correspondingly, significant water-table drawdown may occur in pumping centers co-located with oases, causing oasis loss and environmental impacts.