Surface fires have recently become a widespread pantropical phenomenon that could trigger revolutionary changes in the structure and functioning of tropical forests and result in a catastrophic impoverishment of the vertebrate fauna. Here we describe the short- and medium-term responses of bird and mammal assemblages to an unprecedented wildfire that scorched the understorey of 1,100 km2 of forest in the Arapiuns-Maró river basin of central Brazilian Amazonia. Fire-induced mortality in the aftermath of this burn was high for a wide range of plant and animal populations monitored. This included an average of 36% of all large trees in eight quarter-hectare plots sampled in burnt forest, which dramatically altered the post-burn understorey light environment. The Arapiuns wildfire also resulted in significant socioeconomic costs to local forest dwellers, namely crop losses and the decimation of many forest resources, including key game vertebrate species pursued by subsistence hunters, vines and woody lianas, and many fruit species. The conservation prospects of the vertebrate fauna in fire-prone Amazonian forests are discussed with respect to the increasingly more frequent and severe El Niño-mediated dry seasons.