A cross-sectional model, based on the two dimensional groundwater flow equation of Edelman, was applied at seven transects distributed over four geological cross sections to estimate groundwater heads and recharge from/or groundwater discharge to Lake Nasser. The lake with a length of 500 km and an average width of 12 km was created over the period 1964–1970, the time for constructing the Aswan High Dam (AHD). The model, constrained by regional-scale groundwater flow and groundwater head data in the vicinity of the lake, was successfully calibrated to timeseries of piezometeric heads collected at the cross sections in the period 1965–2004. Inverse modeling yielded high values for the horizontal hydraulic conductivity in the range of 6.0 to 31.1 m day−1 and storage coefficient between 0.01 and 0.40. The results showed the existence of a strong vertical anisotropy of the aquifer. The calibrated horizontal permeability is systematically higher than the vertical permeability (≈1000:1). The calibrated model was used to explore the recharge from/or groundwater discharge to Lake Nasser at the seven transects for a 40-year period, i.e. from 1965 to 2004. The analysis for the last 20-year period, 1985–2004, revealed that recharge from Lake Nasser reduced by 37% compared to the estimates for the first 20-year period, 1965–1984. In the period 1965–2004, seepage of Lake Nasser to the surrounding was estimated at 1.15 × 109 m3 year−1. This led to a significant rise of the groundwater table. Variance-based sensitivity and uncertainty analysis on the Edelman results were conducted applying quasi-Monte Carlo sequences (Latin Hypercube sampling). The maximum standard deviation of the total uncertainty on the groundwater table was 0.88 m at Toshka (west of the lake). The distance from the lake, followed by the storage coefficient and hydraulic conductivity, were identified as the most sensitive parameters. Copyright © 2012 John Wiley & Sons, Ltd.