Regional estimates of evapotranspiration (ET) are needed for environmental analysis and management purposes, yet can be difficult to obtain. Current methods for determining regional ET have spatial, temporal, methodological, and/or logistical limitations that affect their usefulness. To address these gaps, we developed a surface mobile measurement technique, the Regional Evaporative Fraction Energy Balance platform (REFEB), which measures evaporative fraction (EF) and water use efficiency (WUE) using a truck operating on a public right of way. REFEB can measure EF and WUE at 25 or more locations per day, which allows for rapid, dense, and spatially distributed sampling of fields across a region. We assessed the accuracy of the field measurements of EF and WUE with REFEB by comparing them to an Eddy covariance (EC) and Bowen ratio energy balance (BREB) tower. This site validation showed that REFEB has error and uncertainty similar to previous BREB approaches. We then used empirical relationships between field measurements and remote sensing vegetation indices to derive regional maps of EF. We combined these EF maps with satellite observations of net radiation to derive monthly and annual calculations of ET at a 250 m resolution during calendar year 2004 in the Imperial Valley, California, a major agricultural region that is dependent upon irrigation and which has a well constrained water budget. We then summed ET for the Imperial Valley and compared the result to a surface water budget based on irrigation and drainage measurements, which showed good annual and seasonal agreement. These results indicate REFEB produces accurate field measurements of EF and WUE, which can be scaled to estimate regional ET at time scales ranging from less than a week to annual sums.