Arid and semiarid regions are the focus of terrestrial ecological vulnerability as a consequence of their distinctive geography and rapid evolution of anthropogenic controls. To understand the evapotranspiration (ET) variation in ecofragile regions, this study obtained seven years of eddy covariance (EC) observations from the Yulin site in Mu Us Sandy Land, and further proposed a framework to separate the impact of meteorological and anthropogenic controls on ET based on EC observations and Simple Biosphere Model-V2 (SiB2). The observed annual ET ranged from 336 mm·year−1 to 430 mm·year−1. Anthropogenic controls, namely, land cover change into bare soil, alfalfa, and potato, had obvious impacts on ET, which led to − 16.0%, 26.1% and 14.3% of the change in ET during the vegetation-growing period (April-October), respectively. At the annual scale, if alfalfa is planted, ET rises to ~120% that of natural vegetation; if potato is planted, ET remains largely the same. Remarkably, during the crop growing period of potato (June-September), ET of potato rises to ~150% that of natural vegetation. At this ecofragile region, it will take ~ 3–4 years to recover to the natural situation. This study provided a framework for delineating the contribution of meteorological and anthropogenic impacts on ET and a theoretical basis for ecological restoration and vegetation amelioration in semiarid regions.