[Objective] The changes in water use efficiency (WUE) of the Yellow River basin ecosystem and its sensitivity to different environmental factors were analyzed in order to understand the relationship between vegetation restoration, drought, climate conditions, and water resources, thereby providing a theoretical basis for predicting future land surface-atmosphere interactions and dynamic changes of terrestrial ecosystems. [Methods] We calculated WUE in the Yellow River basin and determined the temporal and spatial dynamics of WUE in different land use cover areas by combining the Theil Sen trend method + Mann Kendall test, the Hurst index, partial correlation analysis, a structural equation model, and linear regression residual analysis in the future. We determined the WUE response to temperature vegetation drought index (TVDI), solar radiation (RS), and wind speed (WIN). [Results] ① The spatial distribution of WUE gradually increased from upstream to midstream, and then to downstream. An overall downward trend was dominant. WUE will continue to be dominated by a weakening trend in the future. ② Upstream WUE was positively correlated with WIN and TVDI. RS had no obvious effect on WUE. TVDI and WIN in the middle reaches had a great negative impact on WUE, and RS was conducive to the improvement of WUE. Downstream WUE was mainly negatively affected by WIN and positively affected by RS, while TVDI had no significant effect on WUE. ③ WUE in grassland and unused land areas was positively correlated with RS, and ncgatively correlated with TVDI and WIN. WUE in other areas was positively correlated with RS and TVDI. ④ Changes in WUE in the upstream region of the Yellow River basin were mainly negatively associated with TVDI and WIN. Changes in WUE in the midstream region were mainly positively associated with RS, TVDI, and WIN. Changes in the downstream region were positively associated with TVDI and negatively associated with RS and WIN. [Conclusion] The WUE of the Yellow River basin will be vulnerable to drought and climate factors in the future. Future studies should further analyze the effects of monthly drought and extreme climate on WUE of different land use areas on the basis of climate factors.