Adolescence is a vulnerable period for the development of depressive disorders. Recent research has demonstrated the importance of distress tolerance in the onset and maintenance of depression during adulthood; however, little is known about its role in predicting depressive symptoms among adolescents. The current study examines the effect of distress tolerance and co-occurring negative life events on the developmental trajectory of depressive symptoms from middle to late adolescence. Our sample included 117 adolescent boys and girls (44.4% female, 54.6% White). Participants were, on average, 16 years old at baseline (SD = 0.90) and completed self-report inventories of negative life events and depressive symptoms; distress tolerance was assessed using a behavioral measure. Utilizing a latent growth curve approach, we found a significant interaction between distress tolerance and negative life events in predicting increases in depressive symptoms over time. Follow-up analyses suggest that negative life events were associated with greater increases in depressive symptoms over time for adolescents with lower levels of distress tolerance only. The study highlights the moderating role of distress intolerance in the relation between negative life events and depressive symptoms, and underscores the importance of targeting distress tolerance for treating depression among youth.