The response of potential evapotranspiration (ET0) to widespread irrigation is important to fully understand future regional climate changes and to infer adaptive management of agricultural water resources. The quantitative impact of irrigation on ET0 from 1960 to 2013 was evaluated using historical time series data of daily meteorological observations in the hyper-arid region of northwest China. The decreasing trends in ET0 were accelerated for meteorological stations in regions with oasis agriculture, especially in the summer and during the growing season. Irrigation led to a cooling effect on temperature, increased relative humidity and precipitation. All of these changes contributed to a larger decrease of ET0 trend. The findings of this study advance our insight into the effects of irrigation on dynamics in ET0 and meteorological factors. Further investigations to understand how ET0 responds to climate change and agricultural irrigation could provide guidance for determining effective measures of water resources for adapting to global change.