The semi-arid grasslands in Inner Mongolia (IM) are under increasing stress owing to climate change and rapid socio-economic development in the recent past. We investigated changes in land cover/land use and landscape structure between 1992 and 2004 through the analysis of AVHRR and MODIS derived land cover data. The scale of analysis included the regional level (i.e. the whole of IM) as well as the level of the dominant biomes (i.e. the grassland and desert). We quantified proportional change, rate of change and the changes in class-level landscape metrics using the landscape structure analysis program FRAGSTATS. The dominant land cover types, grassland and barren, 0.47 and 0.27 million km2, respectively, have increased proportionally. Cropland and urban land use also increased to 0.15 million km2 and 2197 km2, respectively. However, the results further indicated increases in both the homogeneity and fragmentation of the landscape. Increasing homogeneity was mainly related to the reduction in minority cover types such as savanna, forests and permanent wetlands and increasing cohesion, aggregation index and clumpy indices. Conversely, increased fragmentation of the landscape was based on the increase in patch density and the interspersion/juxtaposition index (IJI). It is important to note the socio-economic growth in this fragile ecosystem, manifested by an increasing proportion of agricultural and urban land use not just at the regional level but also at the biome level in the context of regional climate change and increasing water stress.