Evapotranspiration (ET) is a vital component in land-atmosphere interactions. In drylands, over 90% of annual rainfall evaporates. The Nile Basin in Africa is about 42% dryland in a region experiencing rapid population growth and development. The relationship of ET with climate, vegetation and land cover in the basin during 2002–2011 is analyzed using thermal-based Simplified Surface Energy Balance Operational (SSEBop) ET, Normalized Difference Vegetation Index (NDVI)-based MODIS Terrestrial (MOD16) ET, MODIS-derived NDVI as a proxy for vegetation productivity and rainfall from Tropical Rainfall Measuring Mission (TRMM). Interannual variability and trends are analyzed using established statistical methods. Analysis based on thermal-based ET revealed that >50% of the study area exhibited negative ET anomalies for 7 years (2009, driest), while >60% exhibited positive ET anomalies for 3 years (2007, wettest). NDVI-based monthly ET correlated strongly (r > 0.77) with vegetation than thermal-based ET (0.52 < r < 0.73) at p < 0.001. Climate-zone averaged thermal-based ET anomalies positively correlated (r = 0.6, p < 0.05) with rainfall in 4 of the 9 investigated climate zones. Thermal-based and NDVI-based ET estimates revealed minor discrepancies over rainfed croplands (60 mm/yr higher for thermal-based ET), but a significant divergence over wetlands (440 mm/yr higher for thermal-based ET). Only 5% of the study area exhibited statistically significant trends in ET.