The occupancy probability of 35 large-bodied bird and mammal species was examined in relation to patch- and landscape-scale habitat and disturbance variables in 147 forest patches distributed throughout the Mexican Yucatán Peninsula. Occupancy was assessed on the basis of interviews with local informants. The most important predictors of vertebrate species richness, composition, and patch occupancy were human population density and the extent and quality of forest cover. Most forest species responded positively to forest extent, while felids in particular were sensitive to human population density. However, the effects of human density on patch occupancy operated at extremely local scales. Effects were stronger at a smaller grain size, offering optimistic prospects for conservation strategies that incorporate human population effects. Three arboreal frugivores (Ateles geoffroyi, Alouatta pigra, and Ramphastos sulfuratus) were strongly associated with total basal area of trees bearing fleshy fruits. The degree of hunting pressure was not related to human population density, and affected the occupancy probability of three game species, two of which (Mazama spp., Crax rubra) are among the most preferred prey across the Yucatán Peninsula. Levels of patch occupancy across this region varied considerably among species, and were best explained by body size and degree of forest habitat specificity, large-bodied species and habitat specialists being the most vulnerable. This study provides a quantitative assessment of the conservation potential of large vertebrates in Mesoamerica and identifies disturbance-sensitive species. This can inform regional-scale conservation planning at a time when low deforestation in parts of the Yucatán Peninsula still provides a narrow window of conservation opportunity given the rapid human population growth.