Nonnative species introductions are becoming more common, but long-term consequences of the novel pressures imposed by invaders on native species remain poorly known. The red imported fire ant, Solenopsis invicta, is an invasive species with potential global impact. Comparison of lizards across the invasive range within the United States reveals novel antipredator strategies and altered morphologies that mitigate potentially lethal attack by these ants, within 70 years of their introduction. The likelihood that adult lizards will behaviorally respond to fire ant attack increases with time since invasion, but hatchlings exhibit high levels of antipredator behavior irrespective of their site of origin. Adults and hatchlings from sites invaded longer ago also have relatively longer hind limbs. This trait increases the effectiveness of behavioral strategies for removing ants and is likely an adaptive response to minimize envenomation during attack. The observed changes are not correlated with habitat, exposure to fire ants, or latitude, arguing against phenotypic plasticity and learning as causal mechanisms, and museum specimens show that morphological differences were not evident prior to fire ant invasion. These data contribute to our growing awareness that ecological invasions can prompt adaptive responses, altering the nature of interactions between invaders and the natives they contact.