Grassland degradation has become an important ecological problem, seriously affecting the social and economic development of northern China. Based on MODIS/NDVI datasets, we analyzed the spatiotemporal patterns of change in vegetation cover and their linkages with climate change and human activities from 2000 to 2015 in the typical grassland region of Xilingol in northern China. The results indicate that NDVI increased significantly, at a growth rate of 0.0021/a. But the trend of vegetation coverage change differed spatially, especially in some areas of northwest Otindag Sandy Land and Sonid Right and Sonid Left Banners, where grassland degradation has occurred. The degraded area accounted for 1/5 of the total, and the grassland vegetation cover in other areas clearly increased. Compared with temperature, precipitation is the main factor affecting vegetation cover change in the study area. Human activities play both a positive and a negative role in improving and degrading grassland vegetation, and the positive effect of human activities on vegetation is greater than the negative effect in Xilingol during 2000- 2015. The area of positive human interference accounted for 34.911% of the total, while human activities led to the destruction of the ecological environment of 19.348% of the area. The returning farmland to forest and grassland program, the Beijing-Tianjin sandstorm source control project, the Three-North shelter forest project, and other ecological engineering programs promoted vegetation coverage growth. However, the rapid development of urbanization and industrialization, overgrazing, excessive land reclamation, and other human activities led to decreased vegetation coverage.