As deforestation frontiers expand in the tropics, understanding species responses is critical to inform efficient land-use management policies. Here we evaluated lizard responses to changes in landscape, habitat patch, and quality in a deforestation frontier in southwestern Brazilian Amazonia. We first considered overall lizard assemblages and then two species subgroups of contrasting thermoregulation strategies. We sampled lizards at 21 forest patches (42–7,035 ha) subject to moderate habitat disturbance (e.g., cattle intrusion and selective logging). Based on 6,000 pitfall trap-days and 60,000 m of visual surveys, we recorded 215 individuals representing 15 species. Contrary to expectations, species richness and abundance were not explained by any of the variables considered, including matrix quality, proportion of forest cover, forest patch area and shape, age since isolation, arthropod biomass, canopy openness, litter volume, tree density, and fire history. However, the composition of persisting species was determined by the structural complexity of the adjacent matrix. The abundance of species that avoid direct sun exposure to regulate their body temperature increased under more-complex structures of adjacent matrix areas and decreased within patches more intensively affected by past fire events. Disturbance within forest patches likely decreased the patch-matrix contrast, contributing to the absence of forest area effects. Nevertheless, species-specific microhabitat requirements dictated part of the lizard species that were able to persist in the fragmented landscape. Strategies aiming to maximize lizard diversity should embrace retention of the habitat quality within forest patches and forest corridors/high-stature vegetation in at least some sites connecting forest remnants.