Deforestation in Amazonia seems likely to continue in the 21st century, and fire risk could increase as a result of global climate change. With deforestation activities providing a source of ignition, the combination of this with increased fire risk could lead to widespread impacts on Amazonian ecosystems. This would also contribute further to climate change through feedbacks on the global carbon cycle. This study uses the McArthur Forest Fire Danger Index and an ensemble of variants of the HadCM3 climate model to simulate potential changes to fire risk in Amazonia over the 21st century. Significant increases in central and eastern Amazonia are simulated by 2020, and high fire danger for over 50% of the forest is simulated in all model runs by 2080. By 2080, as much as 25% of Amazonia shows high levels of agreement in projections of combined fire risk and deforestation. The areas simulated with high fire danger are also those projected to be impacted most significantly by deforestation. If the regional climate changes simulated for Amazonia by HadCM3 are realistic, the risk of significant forest damage could become high, and deforestation activities could, therefore, have a greater potential for impacting on wider areas of forest.