Despite its arid climate, the Egyptian Western Desert is a promising area for development depending on the groundwater, especially the water of the Nubian Sandstone Aquifer System. This article focused on the hydrogeochemical setting of the north-eastern portion of El Farafra Oasis. Groundwater samples from the shallow and the deep zones of the Nubian System were collected and analyzed. A hydrogeochemical evaluation was carried out depending on statistical analyses and bivariate plots. Additionally, Piper, Durov, and Stiff diagrams were also used. The results of factor analysis of the groundwater of the deep zone revealed five factors representing most of the variability of the samples (about 86% variance). Mostly geogenic factors control the ionic compositions of the groundwater, with minor interference of anthropogenic effects. On another side, the hydrogeochemical diagrams of the shallow and deep groundwater indicate that the dominant processes controlling the water chemistry are silicate weathering and possible dissolution of post-Nubian carbonate formations. In terms of water quality, the groundwater needs treatment to be suitable for drinking as a result of high iron concentration, but it showed high suitability for irrigation, livestock, and poultry.