Vegetation is an important component of ecosystems, and it is involved in natural processes such as regional climate circulation, the hydrologic cycle, soil conditions, and other natural processes. It is also an important indicator of regional ecosystem quality change. Aboveground biomass and vegetation cover are important variables for describing vegetation quality and documenting ecosystem changes. Moreover, they are controlling factors in transpiration, photosynthesis, and other terrestrial processes, and are sensitive indicators of land degradation and desertification in arid and semi-arid regions. Aboveground biomass and vegetation cover have been used widely in the analysis of vegetation quality and changes. Inner Mongolia, an important province of northern China that is located mostly in arid and semi-arid areas, is undergoing a process of significant warming and drying, which could lead to serious ecological problems such as land degradation and desertification. Determining the driving cause of these problems has become a focus of vegetation research. Many researchers have attributed the degradation and desertification in northern China to long-term over-grazing, extensive cutting, and widespread conversion of grassland to cropland. Other studies have found that poor climate conditions, such as drought, severe wind erosion, temperature fluctuation, and winter precipitation are the primary cause of degradation and desertification. Nevertheless, some recent studies have shown that human activities can control the degradation in selected study regions of northern China. It is necessary to investigate current ecosystem quality and its response to climatic variation and human activities for a better understanding of the accumulated consèquences of changes in climate and human activities. In this study, combining remote sensing products (aboveground biomass and vegetation cover) with vegetation regionalization data, we quantified ecosystem quality in Inner Mongolia, and analyzed the effects of climate and human activities on spatial variations in quality change from 2000 to 2010. Our results indicated that overall ecosystem quality in Inner Mongolia is very low. Among the ecosystem types, the highest quality was exhibited in forest ecosystems, followed by shrub and grassland ecosystems, respectively. Ecosystem quality displayed evident spatial heterogeneities, divided according to latitude, and reduced gradually from east to west. There was a slight increase in ecosystem quality over the study period. However, degradation and desertification also existed in some regional areas. The spatial variation characteristics of ecosystem quality are formed by interactions between the influencing factors. The partial correlations among ecosystem quality and precipitation, GDP1, fertilizer, the natural forest protection project, and the returning farmland to grassland project were positive and statistically significant. By contrast, ecosystem quality was negatively correlated with temperature, road density, and the treatment of sand and wind sources. With the rapid development of the social economy of Inner Mongolia, the influence of human activities on ecosystem quality gradually increased, but precipitation was still the dominant factor that influenced the spatial variation characteristics of ecosystem quality. The main reasons for the improvement of ecosystem quality in a typical area were increasing precipitation, decreasing temperature, development of agriculture, returning farmland to grassland, and a slowing of traffic development. In addition, decreasing precipitation, increasing temperature, a slowdown of agricultural development, and a speeding up of traffic development led to degradation and desertification. These results provide specific information that may serve to strengthen the necessary public awareness about protecting and restoring ecosystems.