Vegetation coverage directly represents the characteristics and changes in eco-environment in arid regions. Under the background of accelerated climate change and intensified human activities, it is thus urgent to investigate the changes and attributions of vegetation; however, the contributions of different controlling factors have rarely been quantified. Take the Manas River basin as the study area, this study analyzed the temporal and spatial changes of vegetation coverage with NDVI and climate data during the period 1982—2015, and further differentiated the contributions of climate change and human activities to vegetation change. From 1982 to 2015, the spatial pattern of NDVI decreased from the east to the west and from the north to the south. During the past 34 years, the NDVI showed a significant upward trend (+0.60%/10 a), but exhibited interannual variations, and it changed abruptly in 1995. The NDVI increased/decreased significantly before\\after 1995 (+1.50%/10 a and -0.40%/10 a), respectively. Compared with 1982—1995, the vegetation change in 1996—2015 was the combined effects of climate change and human activities. The contributions of climate change and human activities to vegetation change were 52% and 48%, respectively. The method for contribution quantification effectively differentiated the impacts of different factors on vegetation change, and the results showed that it was urgent to implement land management to improve eco-environment in the Manas River basin.