Drosophila melanogaster postfeeding larvae show food-averse migration toward food-free habitats before metamorphosis. This developmental switching from food attraction to aversion is regulated by a neuropeptide Y (NPY)-related brain signaling peptide. We used the fly larva model to delineate the neurobiological basis of age-restricted response to environmental stimuli. Here we provide evidence for a fructose-responsive chemosensory pathway that modulates food-averse migratory and social behaviors. We found that fructose potently elicited larval food-averse behaviors, and painless (pain), a transient receptor potential channel that is responsive to noxious stimuli, was required for the fructose response. A subset of pain-expressing sensory neurons have been identified that show pain-dependent excitation by fructose. Although evolutionarily conserved avoidance mechanisms are widely appreciated for their roles in stress coping and survival, their biological importance in animal physiology and development remains unknown. Our findings demonstrate how an avoidance mechanism is recruited to facilitate animal development.