Many of the sustainability concerns of bioenergy are related to direct or indirect land use change (LUC) resulting from bioenergy feedstock production. The environmental and socio-economic impacts of LUC highly depend on the site-specific biophysical and socio-economic conditions. The objective of this study is to spatiotemporally assess the potential LUC dynamics resulting from an increased biofuel demand, the related greenhouse gas (GHG) emissions, and the potential effect of LUC mitigation measures. This assessment is demonstrated for LUC dynamics in Brazil towards 2030, considering an increase in the global demand for bioethanol as well as other agricultural commodities. The potential effects of three LUC mitigation measures (increased agricultural productivity, shift to second-generation ethanol, and strict conservation policies) are evaluated by using a scenario approach. The novel modelling framework developed consists of the global Computable General Equilibrium model MAGNET, the spatiotemporal land use allocation model PLUC, and a GIS-based carbon module. The modelling simulations illustrate where LUC as a result of an increased global ethanol demand (+26 × 109 L ethanol production in Brazil) is likely to occur. When no measures are taken, sugar cane production is projected to expand mostly at the expense of agricultural land which subsequently leads to the loss of natural vegetation (natural forest and grass and shrubland) in the Cerrado and Amazon. The related losses of above and below ground biomass and soil organic carbon result in the average emission of 26 g CO2-eq/MJ bioethanol. All LUC mitigation measures show potential to reduce the loss of natural vegetation (18%–96%) as well as the LUC-related GHG emissions (7%–60%). Although there are several uncertainties regarding the exact location and magnitude of LUC and related GHG emissions, this study shows that the implementation of LUC mitigation measures could have a substantial contribution to the reduction of LUC-related emissions of bioethanol. However, an integrated approach targeting all land uses is required to obtain substantial and sustained LUC-related GHG emission reductions in general.