A considerable proportion of tropical protected areas are Sustainable Use Reserves (SURs), where socio-biodiversity protection and sustainable resource extraction are the main goals. Subsistence hunting is the most widespread form of subcanopy forest resource extraction, and often depletes game populations within SURs, but the degree to which these extractive activities are sustainable remains questionable. To assess patterns of hunting sustainability within SURs, we systematically examined the local ecological knowledge of 211 resident hunters living in 93 communities located within and immediately outside nine SURs of Brazilian Amazonia. We used mixed models to assess the effects of settlement features (distance to reserve boundaries, size, age, distance to urban centers, and extent of floodplain areas) on local perceptions of game abundance, the prey profile of the most consumed game species, and overall levels of local game depletion. Hunters consistently reported that game populations were less impacted within communal catchment areas containing larger amounts of floodplain habitat and farther from urban centers. In these areas the overall game abundance was perceived to be higher, low-fecundity species were most consumed, and harvest-sensitive species were least depleted. Local SUR communities within this context accrued higher benefits from higher wild-meat availability, but settlement age and size had no effects on hunted species. Evidence-based conservation management plans in tropical protected areas should focus on reducing wild meat demand in urban areas and managing both, the local aquatic animal protein in floodplain areas to relieve pressure on terrestrial game species, and the offtake of game populations at inland sites lacking access to aquatic animal protein.