The arid region of northwest China (ARNC) is the most ecologically fragile region in China, and is characterized by harsh natural conditions, severe soil erosion, and poor soil fertility. Understanding long-term vegetation changes in this region is critical for effective environmental monitoring and climate change adaptation. Fractional vegetation coverage (FVC) is a key parameter for characterizing the ecological conditions of the ARNC. However, the reliance on low-resolution FVC and NDVI data due to the lack of medium-resolution data has limited our understanding of the environmental dynamics in this region. Therefore, this study addressed this gap by utilizing Landsat data to generate FVC data, enabling a detailed investigation of the spatial-temporal variations and driving factors of vegetation in the ARNC from 2000 to 2020. The results indicated the following: (1) The FVC was generally low, with an average of 0.191. The FVC was greater in the northwest and lower in the southeast in terms of spatial distribution features. The trend of FVC change in ARNC showed significant spatial variability, with degradation outweighing improvement. (2) The coefficient of variation of FVC was 0.377, indicating significant temporal fluctuations, with more stable conditions in the northwest than in the southeast. (3) The spatial differentiation of the FVC in ARNC was primarily driven by land cover types, evapotranspiration, and precipitation, with explanatory powers exceeding 30 % each. This study is significant because it provides a comprehensive understanding of vegetation dynamics in one of China's most vulnerable regions, offering critical insights for ecological restoration, desertification control, and sustainable development. The findings underscore the importance of targeted ecological governance to address the challenges posed by environmental degradation in the ARNC.