Taking the Inner Mongolia Autonomous Region as the study area, based on the Pressure-State-Response (PSR) analysis framework and coupled with the spatial distance index model (SDIM), the Land Desertification Sensitivity Evaluation System (LDSES) is constructed. Then combined with the spatio-temporal evolution map of desertification sensitivity, this paper quantitatively discusses the temporal and spatial evolution of land desertification sensitivity in the Inner Mongolia Autonomous Region in 2000, 2005, 2010, 2015 and 2020. At the same time, CA-Markov model is introduced to simulate the future evolution mechanism of desertification sensitivity, and then the geographic detector is used to reveal the characteristics and explanatory power of the main driving factors in the evolution of the first 20 years. The results showed that:(1) the desertification sensitivity of the Inner Mongolia Autonomous Region showed an increasing trend from the northeast to the southwest. Insensitive areas were located in the forest and grassland areas around Great Khingan and Yin Mountains. Highly sensitive areas were located in sandy land and the Gobi Desert such as the Badain Jaran Desert, Tengger Desert, Urumqi Desert, Rambuh Desert, Kubuqi Desert, and Mu Us Desert in the southwest. (2) From the perspective of the temporal and spatial evolution of desertification sensitivity, the areas with improved desertification sensitivity during the study period accounted for 30.65% of the total area. Areas with deteriorating desertification sensitivity accounted for 4.48% of the total area, and areas where the type of desertification sensitivity remained stable accounted for 52.72% of the total area. On the whole, the potential for land desertification is gradually decreasing and the ecological quality of the land was gradually improving. (3) The simulation results of desertification sensitivity in 2030 showed that in the next 10 years, low sensitivity will be the main type (26.43%), the desertification potential will be greatly reduced, and ecological engineering measures will achieve a good result. (4) The driving force analysis showed that the sensitivity of desertification was particularly sensitive to climatic factors, among them, rainfall had the greatest explanatory power for the differentiation of desertification sensitivity. Among the factors of social and economic development, the level of economic development played a major role, indicating that the improvement of economic level would affect the sensitivity of land desertification to a certain extent. And the interaction of various driving factors enhanced the sensitivity of desertification, indicating that the differentiation of desertification sensitivity was the result of a combination of multiple factors. The research can provide reference for the formulation of desertification control and strategies in semi-arid regions.