The current study examines the relation between distress tolerance, perceived stress, and internalizing symptoms across adolescence. Participants included 331 youth, ages 10 to 14 at the first wave of the study, assessed annually over 5 years. A latent growth curve approach was used to test three research questions, including whether perceived stress would increase across adolescence, whether distress tolerance (as measured by a behavioral task) would predict changes in perceived stress, and whether changes in perceived stress would mediate the relation between distress tolerance and internalizing symptoms. Results suggest that, consistent with previous findings, rates of perceived stress do increase across adolescence. Further, findings indicate that distress intolerance at baseline predicted increases in perceived stress, which in turn drove increases in internalizing symptoms. These findings point to the critical role of distress tolerance in bringing about changes in depression and anxiety symptoms and suggest support for utilizing a negative reinforcement framework to understand the emergence of internalizing symptomology.