To address severe grassland degradation problems, China has been implementing a number of national restoration programs, whose significant environmental effect has attracted the attention of many researchers. In this paper, land use and cover change (LUCC) in the Inner Mongolia grassland and the consequent change in net primary productivity (NPP) were studied by combining the land use data of the study area for 2001 and 2009 derived from the MODIS global land cover product and the CASA (Carnegie–Ames–Stanford Approach) model driven with MODIS-NDVI data. The results indicate that the area of Inner Mongolia grassland had a net increase of 77,993 km2 during the study period, which was mainly attributed to the conversion from desert and cropland. The total NPP of Inner Mongolia grassland increased by 29,432.71 Gg C yr− 1 during 2001–2009, of which the human activities and climate change were responsible for 80.23% and 19.77%, respectively. Land conversion and improved management increased grassland NPP directly, and the ecological restoration conducted by large-scale conservation programs could be the intrinsic driving force for this change.