Ample research has shown that low self-esteem increases the risk to develop depressive symptoms during adolescence. However, the mechanism underlying this association remains largely unknown, as well as how long adolescents with low self-esteem remain vulnerable to developing depressive symptoms. Insight into this mechanism may not only result in a better theoretical understanding but also provide directions for possible interventions. To address these gaps in knowledge, we investigated whether self-esteem in early adolescence predicted depressive symptoms in late adolescence and early adulthood. Moreover, we investigated a cascading mediational model, in which we focused on factors that are inherently related to self-esteem and the adolescent developmental period: approach and avoidance motivation and the social factors social contact, social problems, and social support. We used data from four waves of the TRAILS study (Nā=ā2228, 51% girls): early adolescence (mean age 11 years), middle adolescence (mean age 14 years), late adolescence (mean age 16 years), and early adulthood (mean age 22 years). Path-analyses showed that low self-esteem is an enduring vulnerability for developing depressive symptoms. Self-esteem in early adolescence predicted depressive symptoms in late adolescence as well as early adulthood. This association was independently mediated by avoidance motivation and social problems, but not by approach motivation. The effect sizes were relatively small, indicating that having low self-esteem is a vulnerability factor, but does not necessarily predispose adolescents to developing depressive symptoms on their way to adulthood. Our study contributes to the understanding of the mechanisms underlying the association between self-esteem and depressive symptoms, and has identified avoidance motivation and social problems as possible targets for intervention.