Previous studies revealed that low self-esteem is prospectively associated with depression. However, self-esteem has been shown to change over time. We thus hypothesized that not only level but also change in self-esteem affect depression. Using data from a 23-year longitudinal study (N = 1,527), we therefore examined the prospective effects of global and domain-specific self-esteem (physical attractiveness, academic competence) level and change on depressive symptoms 2 decades later. Self-esteem was assessed annually from age 12 to 16, and depression was assessed at age 16 and 35. Results from latent growth curve analyses demonstrated that both level and change in self-esteem served as predictors for adult depression. Individuals who entered adolescence with low self-esteem, and/or whose self-esteem declined further during the adolescent years, were more likely to exhibit symptoms of depression 2 decades later as adults; this pattern held both for global and domain-specific self-esteem. These findings highlight the importance of adolescent self-esteem development for mental health outcomes in adulthood.