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Evapotranspiration is a sensitive parameter for assessing climate change. It controls energy and mass exchange and is a descriptor of drought in arid-and semi-arid regions. Using the Mann-Kendall (M-K) test, Sen’s slope estimator, and the stepwise regression, temporal, and spatial variations in potential evapotranspiration (ET0) and its dominant factors were analysed. The analysis was based on data from 173 meteorological stations in a desertification-prone region of China over the period from 1960 to 2013. The annual ET0 decreased prior to 1990s and increased thereafter. The majority of stations had a decreasing ET0 trend, especially in summer, in which the average slope of all stations was -2.43mmdecade(-1). Analysis of determining factors showed that a decrease in wind speed was the primary factor associated with decreasing ET0. The trend magnitude of ET0 increased from -2.25mmdecade(-1) to -7.43mmdecade(-1) as wind speed increased, then decreased to -3.00mmdecade(-1). Decreasing ET0 and increasing P in the western region led to decrease in the aridity index, suggesting a wetter climate and reduced desertification. Increasing aridity index in the eastern region reduced the vegetation cover and facilitated desertification processes, which might be a disadvantage for ecological reconstruction and desertification control. Better understanding of the response of ET0 to regional climate change may facilitate efficient use of limited water resources and establish management strategies that can combat desertification and maintain ecological security in a desertification-prone region.