The purpose of the multi-measure, multi-wave, longitudinal study was to examine the interactive relation between behavioral distress tolerance (DT) and perceived social support (PSS) in 352 tornado-exposed adolescents aged 12–17 years (M = 14.44; SD = 1.74). At baseline, adolescents completed a computer-based task for DT, and self-report measures of PSS, depressed mood, posttraumatic stress disorder (PTSD), substance use, and interpersonal conflict. Symptoms also were assessed 4 and 12 months after baseline. Findings showed that lower levels of DT together with lower levels of PSS conferred risk for elevated symptoms of prospective depression (t(262) = −2.04, p = .04; reffect size = 0.13) and PTSD (t(195) = −2.08, p = .04; reffect size = 0.15) following a tornado. However, only PSS was significant in substance use t(139) = 2.20, p = .03; reffect size=0.18) and conflict (t(138) = −4.05, p < .0001; reffect size=0.33) in our sample. Implications regarding adolescent DT, the transdiagnostic nature of PSS, and the clinical applications of our findings in the aftermath of a natural disaster are discussed.