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Desertification is one of the major environmental problems that humanity faces today, since it reduces the availability of ecosystem services, increases food insecurity and poverty, and affects the wellbeing of societies. The analysis of the process is extremely complex, since the phenomenon takes place at different temporal and spatial scales, influenced by different factors. It is widely recognized that land use/land cover change (LULC) is one of the main drivers of desertification since environmental degradation is always triggers by the removal of natural vegetation cover. In this study, a LULC change model was calibrated and validated using climate model simulations, demographic data and land susceptibility maps for the historical period 20002010. Then, desertification susceptibility of the Northeast of Brazil were estimated by integrating LULC trajectories with three different downscaled climate change scenarios and projection of population growth for the period 20152025, 20252035, and 20352045 for the emission scenarios RCP4.5 and RCP8.5. Results indicated that, between 2010 and 20352045, areas of moderate susceptibility decreased 10.34%, while areas of high susceptibility increased 12.28% in the case of the RCP4.5. For the RCP8.5 scenario, those numbers are −16.85% for moderate susceptibility, and +19.62% for high susceptibility. Among all indicators included in the analysis, land management was the main driver of desertification susceptibility, which indicates that mitigation and adaptation strategies for the region should pursue sustainable land use policies.