Intensification of anthropogenic activities and related processes have altered the morphology of modern deltaic systems. As a result, mapping of geomorphic features, such as paleochannels, using recently acquired digital elevation data has become increasingly difficult. Using the Nile River and delta as a test site, we developed and applied procedures to map the distribution of paleochannels that existed throughout the Holocene. A high-resolution digital elevation model (DEM) derived from an early, detailed topographic sheet collection was used to minimize the impact of recent man-made topographic artifacts. The DEM-inferred paleochannel distribution was verified using direct and indirect subsurface data. Using our adopted methodology, we identified 76 main and subsidiary paleochannels with a total length exceeding (by >500 km) previously mapped paleochannels. The overwhelming majority (>80%) of the reported historical and archeological sites (29 sites) in the Nile Delta were found to be proximal (<2.5 km) to the identified paleochannels, an observation that is not obvious in any of the previous paleochannel delineations. These observations suggest that the delineated paleochannel distribution of the Nile Delta can be a useful guide for locating ancient cities currently obscured by man-made structures or buried under thick Holocene deposits. Moreover, it can potentially enhance our understanding of the geological and archeological history of the Nile Delta and has societal benefits as these channels could act as preferred pathways for groundwater flow. The advocated methods can be readily applied to river deltas worldwide where high-resolution elevation datasets acquired before the onset of heavy anthropogenic activities are available.