The evolutionary role of fire in animals has been poorly explored. Reptiles use sensory cues, such as smell (chemoreception), to detect threats and flee. In Mediterranean ecosystems, fire is a threat faced by reptiles. We hypothesized that the Mediterranean lizard Psammodromus algirus recognizes the threat of fire by detecting the smoke, which triggers a behavioral response that enhances survival in fire-prone ecosystems. We predicted that lizards from fire-prone ecosystems will be more sensitive to fire stimulus than those from ecosystems that rarely burn. We conducted a terrarium experiment in which lizards from habitats with contrasted fire regimes (fire-prone vs. non-fire-prone) were exposed to smoke versus control (false smoke) treatment. We found that, in populations from fire-prone habitats, more lizards reacted to smoke, and their behavioral response was more intense than in lizard populations from non-fire-prone habitats. Our results suggest that an enhanced response to smoke may be adaptive in lizards from fire-prone ecosystems as it increases the chance for survival. We provide evidence that fire is likely an evolutionary driver shaping behavioral traits in lizard populations exposed to frequent wildfires. Understanding ecological and evolutionary processes shaping animal populations is relevant for species conservation in a changing fire regime world.