Oil palm monoculture comprises one of the most financially attractive land-use options in tropical forests, but cropland suitability overlaps the distribution of many highly threatened vertebrate species. We investigated how forest mammals respond to a landscape mosaic, including mature oil palm plantations and primary forest patches in Eastern Amazonia. Using both line-transect censuses (LTC) and camera-trapping (CT), we quantified the general patterns of mammal community structure and attempted to identify both species life-history traits and the environmental and spatial covariates that govern species intolerance to oil palm monoculture. Considering mammal species richness, abundance, and species composition, oil palm plantations were consistently depauperate compared to the adjacent primary forest, but responses differed between functional groups. The degree of forest habitat dependency was a leading trait, determining compositional dissimilarities across habitats. Considering both the LTC and CT data, distance from the forest-plantation interface had a significant effect on mammal assemblages within each habitat type. Approximately 87% of all species detected within oil palm were never farther than 1300 m from the forest edge. Our study clearly reinforces the notion that conventional oil palm plantations are extremely hostile to native tropical forest biodiversity, which does not bode well given prospects for oil palm expansion in both aging and new Amazonian deforestation frontiers.