Abstract: Grassland change has been a globally concerning issue. Accurately quantifying the trends in grassland resources in the arid region of Xinjiang and their responses to key driving factors is essential for vegetation management in this ecologically fragile area. This study analyzed Leaf Area Index (LAI) data collected during growing seasons from 2001 to 2020 as an indicator for grassland monitoring. We employed multiple analytical methods, including Sen's trend analysis, Mann-Kendall significance test, coefficient of variation, Hurst exponent, and structural equation modeling, to examine the spatiotemporal patterns of Xinjiang grasslands and their responses to topography, climate, and human activities. Spatial analysis revealed significant heterogeneity in Xinjiang grasslands. The multi-year average LAI value from 2001 to 2020 was 0.37 m²/m², characterized by higher values in the north and west, and lower values in the south and east. During the study period, LAI exhibited a fluctuating upward trend with an average annual growth rate of 0.003 yr⁻¹. Trend analysis indicated that approximately 67.3% of the areas showed improvement, while 19.2% experienced degradation, with the degraded areas primarily concentrated in the vicinity of the Ili River Valley and Tacheng Prefecture. Furthermore, the structural equation model revealed that topography, climate, and livestock factors substantially impacted the spatial distribution of LAI in Xinjiang grasslands. Precipitation and wind speed were identified as the dominant factors affecting LAI, with total path coefficients of 0.34 and −0.32, respectively. Topography, through its interactions with climate and livestock numbers, exerted a significant positive impact on LAI. Overall, precipitation, altitude, and livestock numbers demonstrated positive influences, whereas wind speed, temperature, and solar radiation exhibited negative effects. Between 2001 and 2020, the LAI of Xinjiang grasslands displayed marked fluctuations, primarily attributed to the combined effects of natural environmental and human activity factors.