The Shule River Basin (SRB) is a typical arid area in northwest China with a fragile ecology. Un-derstanding vegetation dynamics and its response to climate change and human activities provides essential information for ecological and environmental resource management. This study extracted fractional vegetation coverage (FVC) data from 2000 to 2019 using the Google Earth Engine plat-form and Landsat satellite images, employing trend analysis and other methods to examine spati-otemporal changes in vegetation in the SRB. Additionally, partial correlation and residual analysis were utilized to explore the response of FVC to climate change and human activities. The main results were as follows: (1) The regional average FVC in the SRB showed a significant upward trend from 2000 to 2019, increasing by 1.3 × 10−3 y–1. The area within 1 km of roads experienced a higher increase of 3 × 10−3 y–1, while the roadless areas experienced a lower increase of 1.1 × 10−3 y–1. Road construction from 2004 to 2006 significantly reduced the FVC within 200 meters of the roads. FVC spatial heterogeneity in the SRB is significant. (2) Partial correlation analysis shows that FVC has a strong positive correlation with precipitation and surface water area, with correlation coefficients of 0.575 and 0.744, respectively. There is a weak negative correlation between FVC and land surface temperature (LST). FVC changes are more influenced by precipitation than by LST. (3) Compared to climate factors, human activities have a greater impact on vegetation dynamics in the SRB. The contributions of climate change to vegetation recovery are increasing. (4) The area changes of dif-ferent land types are closely related to climate factors and human activities, reflecting their impact on vegetation. These results provide valuable information for ecosystem restoration and environ-mental protection in the SRB.