Ecosystem water use efficiency (eWUE) is a useful metric to examine the interactions between water and carbon cycles in ecosystems. To reveal the response and adaptation characteristics of different vegetation types within the context of global warming on a regional scale, the spatiotemporal characteristics and influencing factors of the seasonal eWUE of various vegetation types in Inner Mongolia from 2001 to 2020 were explored. Based on MODIS gross primary productivity (GPP), evapotranspiration (ET) data and meteorological data, in this study, we estimated eWUE in different seasons in Inner Mongolia and used trend analysis and correlation analysis methods to analyze the relationship between eWUE in spring, summer and autumn and the temperature–precipitation. From 2001 to 2020, in this region, the GPP and ET in spring, summer and autumn showed increasing trends. In addition, the growth rates of GPP and ET in spring and summer were higher than those in autumn. Under the combined effect of GPP and ET, eWUE in different seasons showed a significant decreasing trend (p < 0.05)—this is ascribed to the extent of ET increasing more than GPP, especially in summer, with the most obvious decreasing rate. In terms of spatial trend, in spring and summer, there is a decreasing trend from northeast to southwest. The effects of precipitation and temperature on the eWUE in Inner Mongolia were mainly negatively correlated in the northeastern part of Inner Mongolia with higher altitudes during the spring and autumn seasons. In total, 95.096% of the total area had positive correlations between eWUE and temperature in spring. In summer, the region in which the WUE of the vegetation had an inverse relationship with both the temperature and the amount of precipitation was the largest compared to these regions in spring and autumn. © 2022 by the authors.