As the main component of terrestrial ecosystem, vegetation plays a very important role in regional ecosystem environmental change, global carbon cycle, and climate regulation. The Nujiang-Salween River Basin is one of the most important transboundary rivers in Southeast Asia, and its vegetation changes will affect regional ecosystems and climate. This study takes the Nujiang-Salween River Basin as the research area, based on the MODIS NDVI data from 2000 to 2021, using the BFAST model, Hurst exponent, and geographic detectors to study the temporal and spatial evolution trends of vegetation coverage, future sustainability, and driving factors. The results show that:(1) from 2000 to 2021, the vegetation coverage of the Nujiang-Salween River Basin presented an overall fluctuating upward trend, and the annual average Fractional Vegetation Cover (FVC) value was 0.73, mainly with high vegetation coverage and relatively high vegetation coverage. Vegetation distribution had obviously spatial heterogeneity, and the vegetation coverage in the lower and middle reaches was significantly larger than that in the upper reaches. (2) The BFAST trend indicated that in the past 22 years, the proportions of areas with improved and degraded vegetation cover in the Nujiang-Salween River Basin were 71.24% and 28.76%, respectively. The improved areas were much larger than the degraded areas, indicating that the vegetation in the study area has been well protected. The Hurst exponent shows that the proportion of areas where vegetation will continue to improve and degrade in the future is 94.89% and 2.76%, respectively. The superposition of BFAST and Hurst coupled 17 types of future trends in vegetation coverage. Overall, the vegetation in the future will continue to improve, accounting for 68.99% and 29.09% of the areas that will continue to improve and continue to degrade, respectively. (3) The results of Optimal Parameters-based Geographic Detector (OPGD) show that altitude has a macroscopic control effect on the distribution of vegetation coverage in the study area, with the greatest impact, followed by meteorological factors such as temperature and precipitation. There are differences in the influencing factors of vegetation cover among different regions. The altitude and land use methods have more significant impact on vegetation cover in the upper reaches than in the lower and middle reaches. In the alpine and canyon regions of the middle reaches, the altitude and differences in temperature and precipitation brought about by altitude have major impact on vegetation coverage, while the lower reaches is mainly influenced by factors such as population and GDP. The results provide scientific data support for understanding the ecological environment status and future changes in the research area.