Fires in South America cause forest degradation and contribute to carbon emissions associated with land use change. We investigated the relationship between year-to-year changes in fire activity in South America and sea surface temperatures. We found that the Oceanic Niño Index was correlated with interannual fire activity in the eastern Amazon, whereas the Atlantic Multidecadal Oscillation index was more closely linked with fires in the southern and southwestern Amazon. Combining these two climate indices, we developed an empirical model to forecast regional fire season severity with lead times of 3 to 5 months. Our approach may contribute to the development of an early warning system for anticipating the vulnerability of Amazon forests to fires, thus enabling more effective management with benefits for climate and air quality.