Background Although it is known that atopic dermatitis (AD) can develop during adolescence, research on its course and predictors in this age group is thus far limited. Objective We aimed to describe the course of AD over puberty and prospectively determine risk factors for the incidence, recurrence, and persistence of AD until adolescence in a population-based cohort study. Methods German participants of the International Study of Asthma and Allergies in Childhood Phase II were followed prospectively. The final dataset comprised 2857 adolescents, of whom 2433 were unaffected by AD at baseline. Bivariate and multivariate prediction models for the incidence, recurrence, and persistence of AD using early-life factors, family history of atopic diseases, and job history as predictors were developed. Results The incidence of AD between ages 9 to 11 and 16 to 20 years was 1.7%, and recurrence was 2.4%. AD persisted in 47.6% of adolescents with AD symptoms at baseline (n = 424). High socioeconomic status, female sex, asthma symptoms and a positive skin prick test response at baseline, parental history of rhinitis/AD, and having worked in a high-risk job were significant predictors for the course of disease. With all the factors present, the probability of the incidence of AD was 21.4% (95% CI, 1.8% to 80.2%) and increased up to 81.7% (95% CI, 47.0% to 95.8%) for recurrence of AD and 87.6% (95% CI, 63.4% to 96.6%) for persistence of AD among those affected by AD. Early-life exposures did not predict the course of AD over puberty. Conclusion Genetic factors, early allergen sensitization, and having worked in a high-risk job seem to be more important for disease development in late adolescence than other early-life exposures.