Contains datasets for flight behaviors by Sceloporus undulatus in response to native ants and an avian predator as well as injury frequencies at fire ant invaded and uninvaded sites. Many complex behavioral responses of animals to environmental cues (potential mates, predators, food) are governed by general “rules of thumb”. Many animals thus respond in the same way to a range of stimuli (e.g. flee from any looming object). Animals that face novel conditions as a result of global environmental change may need to alter these behavioral rules in order to persist. However, adaptation of generalized behavioral rules to novel selective pressures may cause a species to be maladapted to original conditions, such as predators, that remain in its environment. Invasive fire ants (Solenopsis invicta) are novel venomous predators of Eastern Fence Lizards (Sceloporus undulatus). Lizards from fire ant-invaded sites break their crypsis to flee from encounters with fire ants at higher frequencies than do fire ant naïve lizards. This behavioral shift promotes escape from and survival of attacks by these invasive ants but could incur reduced survival by attracting native visual predators. Generalization of this increased flight behavior to native species could further increase this cost. We tested whether lizards’ increased propensity to flee from fire ants following their invasion is generalized to native ants and a predatory bird. We found that the increased behavioral responsiveness to fire ants was also exhibited in response to staged encounters with two native ant species, but did not carry-over to affect responses to a perceived avian predator (a taxidermied American Kestrel). We also found evidence of a potential cost of this behavioral change: lizards from populations invaded by fire ants had higher injury rates, which likely indicate greater attempted predation. This suggests generalized anti-ant behavior may improve survival in the presence of fire ants but increase detection and attacks by native visual predators. Together, the results of this study contribute to our understanding of both the consequences and limitations of rapid adaptation.