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Paleoclimatic regimes over Saharan Africa alternated between dry and wet periods throughout the Pleistocene Epoch, and it is during the wet periods that the Saharan fossil aquifers were recharged. We investigated the role of groundwater-related processes in shaping the Saharan landforms (e.g., theater-headed valleys [THV]; depressions, escarpments, playas, and tufa deposits) over areas occupied by the largest of these aquifer systems, the Nubian Sandstone Aquifer System (NSAS; area: 2.6 million km2) in Egypt, Libya, Sudan, and Chad. We reviewed the suggested hypotheses for the origin of these landforms in the Sahara and in similar settings elsewhere and present evidence (remote sensing-based landscape analysis, geostatistical and geospatial analyses, hydrological, lithological, isotopic and field) in support of the following: in Pleistocene wet periods groundwater under high hydrostatic pressures accessed deep-seated structures, discharged at the free faces, THV developed, scarps retreated, fluvial (in wet periods) and aeolian processes (in dry periods) together with seepage weathering eroded and transported loose debris, and depressions were formed. Evidence includes: (1) extensive distribution of THV (stubby-looking geometry, theater-like heads, U-shaped profiles, flat floors, and structurally controlled patterns) indicative of sapping processes were mapped (using a GIS-based logistic regression model) along faulted scarps extending for over 1450 km in the NSAS; (2) widespread distribution of tufa deposits plastered on scarp faces of the natural depressions within the NSAS with isotopic compositions consistent with deposition from NSAS fossil groundwater (δ18O: − 12.8 to − 8.0‰); (3) absence of well-developed drainage systems over the Libyan Plateau; (4) onset of endorheic streams from the identified THV along the NSAS escarpments (within the Qattara, Kharga, Farafra, and Dakhla depressions) and at the boundary between massive limestone formations (e.g., Gara, Kurkur, and Marmarica) and underlying erodible shale and argillaceous sandstone formations (e.g., Dakhla and Moghra) consistent with a groundwater discharge origin for the endorheic streams; (5) reported carbonate-rich playa deposits within scarp-foot depressions at the terminations of the endorheic streams; (6) artesian upward leakage of depleted NSAS groundwater (δD: − 81 to − 72‰; and δ18O: − 12.8 to − 8.0‰) into shallower Oligocene, Miocene, and Pliocene aquifers (δD: − 0.7 to 7.2‰; δ18O: − 1.13 to 1.20‰) as evidenced by the mixed isotopic composition (δD range: − 62.6 to − 2.6‰; δ18O range: − 7.0 to − 1.09‰) of groundwater. Understanding the role of groundwater processes in landscape evolution over areas occupied by the NSAS has implications for understanding the development of landscape in Saharan Africa, Arabian Sahara, similar settings worldwide, and the evolution of the Martian landscape.