SummaryMedium- and large-sized mammals play important roles in maintaining forest ecosystem functions, and these functions often diminish when mammal species are depleted by human activities. Understanding the sensitivity or tolerance of mammal species to human pressure and detecting species changes through monitoring programmes can inform appropriate management decisions. The objective of our study was to identify medium- and large-sized mammal species that can be included in a monitoring programme in the Southern Yungas of Argentina. We used occupancy modelling to estimate the probability of habitat use (ψ) of 13 of 25 mammal species detected by 165 camera traps placed in forests across a range of human footprint index (HFI) values. As defined by the HFI, 54% of the study area is wilderness. The probabilities of habitat use of two mammal species were significantly associated with the HFI: the lowland tapir (Tapirus terrestris; ψ = 0.33, range = 0.22–0.50) was inversely associated with HFI values, whereas the grey brocket deer (Mazama gouazoubira; ψ = 0.79, range = 0.67–0.87) was positively associated with the HFI. Monitoring the probability of habitat use of the sensitive species (lowland tapir) could help us to detect changes in areas experiencing anthropogenic impacts before they cause extirpation, whereas the high probability of the habitat use values of the tolerant species (grey brocket deer) might indicate that anthropogenic impacts are strongly influencing habitat, signalling that mitigation strategies might be warranted. The Southern Yungas retains an intact mammal fauna, and we showed that the HFI is useful for monitoring anthropogenic impacts on these mammals. There are still opportunities to develop conservation strategies to minimize threats to mammal species in the region by implementing a monitoring programme with the proposed species.