Kiseiba Oasis and depression are located in southern Egypt between the Selima Sand Sheet to the west and the Nile to the east, an important area that hosted Late Cenozoic drainage, Middle Pleistocene lakes, and numerous Paleolithic and Neolithic cultural sites. A synthesis of orbital data, field surveying and near-surface stratigraphy provides new insights into the Quaternary history of this region. Shuttle Imaging Radar data show a complex of fluvial channels that are due to stringers of surficial fluvial lag, subsurface fluvial deposits, and areas of deep alluvium. Three topographic surfaces are described: 1) the Atmur El-Kibeish, above 230 m elevation, which displays a linear pattern of light radar returns, possibly formed from northeast drainage; 2) the Acheulean Surface, at 200 m elevation, that has dark radar patterns resulting from thick alluvium bounded by pebble sand and calcrete strata, and 3) the Kiseiba Surface, below 190 m, that has a complex series of surface and subsurface fluvial and aeolian sediments. Initial drainage from the Early through Middle Pleistocene was to the northeast, which may have lasted through the Last Interglacial. Later reworking of sediments during the Last Glacial Maximum and the Holocene resulted in topographic inversion, with any subsequent local drainage on the Kiseiba Surface to the southwest, towards the Kiseiba Scarp.