The irrigated Indus Basin in Pakistan has insufficient water resources to supply all its stakeholders. Information on evaporative depletion across the Basin is an important requirement if the water resources are to be managed efficiently. This paper presents the Surface Energy Balance Algorithm for Land (SEBAL) method used to compute actual evapotranspiration for large areas based on public domain National Oceanic and Atmospheric Administration (NOAA) satellite data. Computational procedures for retrieving actual evapotranspiration from satellites have been developed over the last 20 years. The current work is among the first applications used to estimate actual evapotranspiration on an annual scale across a vast river basin system with a minimum of ground data. Only sunshine duration and wind speed are required as input data for the remote sensing flux algorithm. The results were validated in the Indus Basin by comparing results from a field-scale transient moisture flow model, in situ Bowen ratio measurements, and residual water balance analyses for an area of 3 million ha. The accuracy of assessing time-integrated actual annual evapotranspiration varied from 0% to 10% on a field scale to 5% at the regional level. Spatiotemporal information on actual evapotranspiration helps to evaluate water distribution and water use between large irrigation project areas. Wide variations in evaporative depletion between project areas and crop types were found. Satellite-based measurements can provide such information and avoid the need to rely on field databases.