Habitat fragmentation has been shown to influence the abundance, movements and persistence of many species. Here, we examine the effects of forest patch and landscape metrics, and levels of forest disturbance on the patterns of local extinction of five primate and 14 carnivore species within 129 forest patches in a highly fragmented forest landscape of southern Brazilian Amazonia. Classic habitat area effects were the strongest predictors of species persistence, explaining between 42% and 55% of the overall variation in primate and carnivore species richness. Logistic regression models showed that anthropogenic disturbance, including surface wildfires, timber extraction and hunting pressure, had detrimental effects on the persistence of some species over and above those of fragment size. Different species ranged in their responses from highly sensitive to highly tolerant to forest fragmentation. Patterns of local extinction documented here were by no means chance events, and the nestedness of the overall species-by-site matrix was highly nonrandom in terms of the sets of species extirpated from the most to the least species-rich forest patches.