Abstract: Fractional vegetation cover (FVC) represents a key indicator for quantifying the situation of surface vegetation, and its spatiotemporal heterogeneity is of great significance for ecological conservation and regional sustainable development. Based on the normalized difference vegetation index (NDVI) data spanning from 2001 to 2022, this study quantitatively revealed the long-time-series spatial differentiation pattern of FVC and its driving factors in the Yarlung Zangbo River basin using a range of methods, including Theil-Sen Median trend analysis, Mann-Kendall test, optimal parameters-based geographical detector (OPGD), and partial correlation analysis. The results indicate that from 2001 to 2022, the FVC of the basin showed a pronounced upward trend and distinct spatial heterogeneity. Specifically, 61.83% and 6.18% of the basin exhibited improved and degraded vegetation cover (β≥0.000 5; β≤-0.000 5), respectively, while the vegetation cover remained stable in 31.99% of the basin. The mean interannual coefficient of variation was determined at 0.023 4, suggesting slight fluctuations overall, with significant variations observed in only 0.28% of the basin. Elevation, annual average temperature, annual precipitation, and land use type were identified as primary factors controlling the spatial differentiation of FVC. Meanwhile, the interactions between land use type and elevation and between population density and slope aspect demonstrated the strongest and weakest explanatory power, respectively, with q values of 0.794 31 and 0.015 18. Additionally, there existed a weak positive correlation between FVC and temperature (average partial correlation coefficient: 0.12), with the warming effect promoting vegetation growth in 67.74% of the basin. In contrast, the impacts of precipitation on FVC varied spatially. Specifically, increased precipitation contributed to elevated FVC in the central and western arid parts, exerted a minimal impact on FVC in most humid regions in the eastern part, and presented a positive correlation with the indicator in Motuo County of Linzhi City and its surrounding areas. The results of this study reveal the spatiotemporal evolution patterns of FVC and their driving factors in the Yarlung Zangbo River basin, providing a scientific basis for ecological protection and sustainable development planning in alpine river basins.