There is a general agreement that deep aquifers experience significant lag time in their response to climatic variations. Analysis of Temporal Gravity Recovery and Climate Experiment (GRACE), Soil Moisture and Ocean Salinity mission (SMOS), satellite altimetry, stable isotopic composition of groundwater, and precipitation and static global geopotential models over the Nubian Sandstone Aquifer System (NSAS) revealed rapid aquifer response to climate variability. Findings include: (1) The recharge areas of the NSAS (Northern Sudan Platform subbasin) witnessed a dry period (2002-2012), where average annual precipitation (AAP) was modest (85 mm) followed by a wet period (2013-2016; AAP: 107 mm), and during both periods the AAP remained negligible (280 km from source areas) and in soil moisture content in areas with shallow (<2 m) groundwater levels to fluctuations in Lake Nasser surface water, and (2) the isotopic composition (O, H) of groundwater along the preferred pathways, consistent with mixing of enriched (Lake Nasser water or precipitation over Sudan) and depleted (NSAS fossil water) endmembers. Findings provide new insights into the response of large, deep aquifers to climate variability and address the sustainability of the NSAS and similar fossil aquifers worldwide.