Highly productive wells in the Central Eastern Desert of Egypt are tapping groundwater in subsided blocks of Jurassic to Cretaceous sandstone (Taref Formation of the Nubian Sandstone Group) and Oligocene to Miocene sandstone (Nakheil Formation), now occurring beneath the Red Sea coastal plain and within the proximal basement complex. Aquifer development is related to Red Sea rifting: (1) rifting was accommodated by vertical extensional displacement on preexisting NW-SE– to N-S–trending faults forming a complex array of half-grabens and asymmetric horsts; and (2) subsided blocks escaped erosion accompanying the Red Sea–related uplift. Subsided blocks were identified and verified using satellite data, geologic maps, and field and geophysical investigations. Interpretations of very low frequency (VLF) measurements suggest the faults acted as conduits for ascending groundwater from the subsided aquifers. Stable isotopic compositions (δD: –19.3‰ to –53.9‰; δ18O: –2.7‰ to –7.1‰) of groundwater samples from these aquifers are interpreted as mixtures of fossil (up to 70%) and modern (up to 65%) precipitation. Groundwater volumes in subsided blocks are large; within the Central Eastern Desert basement complex alone, they are estimated at 3 × 109 m3 and 10 × 109 m3 for the Nakheil and Taref Formations, respectively. Results highlight the potential for identifying similar rift-related aquifer systems along the Red Sea–Gulf of Suez system, and in rift systems elsewhere. An understanding of the distribution of Red Sea rift–related aquifers and modern recharge contributions to these aquifers could assist in addressing the rising demands for fresh water supplies and water scarcity issues in the region.