Few researchers have investigated the synergistic effects of tropical forest fragmentation and disturbance on species persistence and abundance. We examined effects of both forest-patch metrics and forest disturbance in determining richness and abundance of midsized to large-bodied mammal species in a highly fragmented Amazonian forest landscape. Twenty-one forest fragments, ranging from 2 to 14,480 ha, and two continuous forest sites were sampled based on sightings, tracks, line-transect censuses, armadillo burrow censuses, and camera trapping. Patch occupancy of 37 species recorded ranged from 4% to all forest sites surveyed. Forest fragment size was the strongest predictor of species persistence, explaining 90% of the variation in species richness. Information-theoretic analysis confirmed that fragment area was the most important explanatory variable for the overall species richness and abundance of mammal species, followed by surface fires, which affected the abundance of seven species. Large mammal species were typically absent from fragments <100 ha, whereas some ubiquitous species were favored by fragmentation, exhibiting hyperabundance in small patches. Our findings highlight the importance of large (>10,000 ha), relatively undisturbed forest patches to maximize persistence and maintain baseline abundances of Neotropical forest mammal species.