Fires in tropical forests release globally significant amounts of carbon to the atmosphere and may increase in importance as a result of climate change. Despite the striking impacts of fire on tropical ecosystems, the paucity of robust spatial models of forest fire still hampers our ability to simulate tropical forest fire regimes today and in the future. Here we present a probabilistic model of human-induced fire occurrence for the Amazon that integrates the effects of a series of anthropogenic factors with climatic conditions described by vapor pressure deficit. The model was calibrated using NOAA-12 night satellite hot pixels for 2003 and validated for the years 2002, 2004, and 2005. Assessment of the fire risk map yielded fitness values > 85% for all months from 2002 to 2005. Simulated fires exhibited high overlap with NOAA-12 hot pixels regarding both spatial and temporal distributions, showing a spatial fit of 50% within a radius of 11 km and a maximum yearly frequency deviation of 15%. We applied this model to simulate fire regimes in the Amazon until 2050 using IPCC's A2 scenario climate data from the Hadley Centre model and a business-as-usual (BAU) scenario of deforestation and road expansion from SimAmazonia. Results show that the combination of these scenarios may double forest fire occurrence outside protected areas (PAs) in years of extreme drought, expanding the risk of fire even to the northwestern Amazon by midcentury. In particular, forest fires may increase substantially across southern and southwestern Amazon, especially along the highways slated for paving and in agricultural zones. Committed emissions from Amazon forest fires and deforestation under a scenario of global warming and uncurbed deforestation may amount to 21 +/- 4 Pg of carbon by 2050. BAU deforestation may increase fires occurrence outside PAs by 19% over the next four decades, while climate change alone may account for a 12% increase. In turn, the combination of climate change and deforestation would boost fire occurrence outside PAs by half during this period. Our modeling results, therefore, confirm the synergy between the two Ds of REDD (Reducing Emissions from Deforestation and Forest Degradation in Developing Countries).