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Climate change scenarios vary considerably over the Amazon region, with an extreme scenario projecting a dangerous (from the human perspective) increase of 3.8°C in temperature and 30% reduction in precipitation by 2050. The impacts of such climate change on Amazonian land-use dynamics, agricultural production, and deforestation rates are still to be determined. In this study, the authors make a first attempt to assess these impacts through a systemic approach, using a spatially explicit modeling framework to project crop yield and land-use/land-cover changes in the Brazilian Amazon by 2050. The results show that, without any adaptation, climate change may exert a critical impact on the yields of crops commonly cultivated in the Amazon (e.g., soybean yields are reduced by 44% in the worst-case scenario). Therefore, following baseline projections on crop and livestock production, a scenario of severe regional climate change would cause additional deforestation of 181 000 km2 (+20%) in the Amazon and 240 000 km2 (+273%) in the Cerrado compared to a scenario of moderate climate change. Putting an end to deforestation in the Brazilian Amazon forest by 2020 (and of the Cerrado by 2025) would require either a reduction of 26%–40% in livestock production until 2050 or a doubling of average livestock density from 0.74 to 1.46 head per hectare. These results suggest that (i) climate change can affect land use in ways not previously explored, such as the reduction of yields entailing further deforestation, and (ii) there is a need for an integrated/multidisciplinary plan for adaptation to climate change in the Amazon.