Abstract: The northern slope of Tianshan Mountains is an important ecological functional area and a major economic zone in Northwest China. Due to the impacts of climate change and human activities, its fragile ecological environment has been facing great challenges, whereas there is limited knowledge of spatiotemporal changes, characteristics, and driving forces of ecological environment quality in this region. Therefore, this paper utilizes the enhanced remote sensing ecological index (ERSEI), spatial autocorrelation analysis, multivariable linear regression model, and geographically weighted analysis to reveal the spatiotemporal changes, characteristics, and driving factors of ecological environment quality on the north slope of Tianshan Mountains in four periods: 1990, 2000, 2010, and 2020. The results show that: (1) from 1990 to 2020, the ERSEI of the north slope of Tianshan Mountains first significantly declined, then gradually recovered and continued to rise. The ecological environment quality gradually improved and tended to be stable, with an overall spatial pattern of "superior in the east and inferior in the west"; (2) the ecological environment of the north slope of the Tianshan Mountains is more sensitive to climate change, and temperature is the most important driving factor for the change of ERSEI; (3) There is significant spatial heterogeneity in the effects of different driving factors on ERSEI. Natural factors play a dominant role in local spatial variability, while anthropogenic factors exert an important influence on the interannual variability. This suggests that climate change and human activities have significantly affected ERSEI changes. In the future, various economic activities should be scientifically planned to mitigate the effects of climate change, and enhance the ecological security and environmental sustainability of the north slope of the Tianshan Mountains.