Landscape‐scale deforestation poses a major threat to global biodiversity, not only because it limits habitat availability, but also because it can drive the degradation of the remaining habitat. However, the multiple pathways by which deforestation directly and indirectly affects wildlife remain poorly understood, especially for elusive forest‐dependent species such as arboreal mammals. Using structural equation models, we assessed the direct and indirect effects of landscape forest loss on arboreal mammal assemblages in the Lacandona rainforest, Mexico. We placed camera traps in 100 canopy trees, and assessed the direct effect of forest cover and their indirect effects via changes in tree basal area and canopy openness on the abundance and diversity (i.e., species richness and exponential of Shannon entropy) of arboreal mammals. We found that forest loss had negative indirect effects on mammal richness through the increase of tree canopy openness. This could be related to the fact that canopy openness is usually inversely related to resource availability and canopy connectivity for arboreal mammals. Furthermore, independently of forest loss, the abundance and richness of arboreal mammals was positively related to tree basal area, which is typically higher in old‐growth forests. Thus, our findings suggest that arboreal mammals generally prefer old‐growth vegetation with relatively low canopy openness and high tree basal area. However, unexpectedly, forest loss was directly and positively related to the abundance and richness of mammals, probably due to a crowding effect, a reasonable possibility given the relatively short history (~40 years) of deforestation in the study region. Conversely, the Shannon diversity was not affected by the predictors we evaluated, suggesting that rare mammals (not the common species) are the ones most affected by these changes. All in all, our findings emphasize that conservation measures ought to focus on increasing forest cover in the landscape, and preventing the loss of large trees in the remaining forest patches.