Land use and hunting are 2 major pressures on biodiversity in the tropics. Yet, their combined impacts have not been systematically quantified at a large scale. We estimated the effects of both pressures on the distributions of 1884 tropical mammal species by integrating species' range maps, detailed land-use maps (1992 and 2015), species-specific habitat preference data, and a hunting pressure model. We further identified areas where the combined impacts were greatest (hotspots) and least (coolspots) to determine priority areas for mitigation or prevention of the pressures. Land use was the main driver of reduced distribution of all mammal species considered. Yet, hunting pressure caused additional reductions in large-bodied species' distributions. Together, land use and hunting reduced distributions of species by 41% (SD 30) on average (year 2015). Overlap between impacts was only 2% on average. Land use contributed more to the loss of distribution (39% on average) than hunting (4% on average). However, hunting reduced the distribution of large mammals by 29% on average; hence, large mammals lost a disproportional amount of area due to the combination of both pressures. Gran Chaco, the Atlantic Forest, and Thailand had high levels of impact across the species (hotspots of area loss). In contrast, the Amazon and Congo Basins, the Guianas, and Borneo had relatively low levels of impact (coolspots of area loss). Overall, hunting pressure and human land use increased from 1992 to 2015 and corresponding losses in distribution increased from 38% to 41% on average across the species. To effectively protect tropical mammals, conservation policies should address both pressures simultaneously because their effects are highly complementary. Our spatially detailed and species-specific results may support future national and global conservation agendas, including the design of post-2020 protected area targets and strategies.