Human land transformation alters features of the landscape that may favor or eliminate biodiversity. Understanding habitat use among species in human-affected ecosystems can inform the management of habitats and conservation of species. The Trans-Mexican Volcanic Belt in central Mexico is a biological hot spot for lizard species diversity that is under considerable anthropogenic pressures including grazing, agriculture, urbanization, and climate change. Here, we used species-occupancy modeling to (1) identify habitat characteristics that are essential to predicting the presence of Sceloporus torquatus and S. grammicus lizards, (2) determine if disturbance predicts species occupancy, and (3) determine which features, if any, predict our ability to detect each species in the wild. We found that S. torquatus lizards were more likely to be present in areas with large boulders and abundant refuges, whereas S. grammicus lizards were more common in forests with leaf litter. Human disturbance and urban disruption did not predict the occupancy of either species, with lizards making use of artificial as well as natural refuges in human settlements as well as protected areas. Although we found only weak evidence that habitat and climate predicted detection probabilities, Sceloporus lizards (particularly S. grammicus) were somewhat more easily detected in high humidity, perhaps because of generally higher activity levels. Our results emphasize the importance of understanding the detailed physical characteristics that allow each species to persist, even in disturbed habitats. This can better inform conservation efforts so that resources are allocated to ensure that these characteristics, like rocks and trees, are readily available in both pristine and human-modified areas.