IMPORTANCE: Research has highlighted associations between atopic dermatitis (AD) and mental health conditions in adults. However, literature on the development of mental health comorbidities in children is limited despite the large burden of pediatric AD worldwide. OBJECTIVE: To examine the association between AD and internalizing behaviors and symptoms of depression at multiple points across childhood and adolescence and to explore potential mediating factors, including asthma/rhinitis, sleep, and inflammation. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, population-based birth cohort study included children followed up from birth for a mean (SD) duration of 10.0 (2.9) years from the UK Avon Longitudinal Study of Parents and Children. Data were collected from September 6, 1990, to December 31, 2009. Data were analyzed from August 30, 2019, to July 30, 2020. EXPOSURES: Annual period prevalence of AD assessed at 11 points from 6 months to 18 years of age, measured by standardized questions about flexural dermatitis. MAIN OUTCOMES AND MEASURES: Symptoms of depression, measured using child-reported responses to the Short Moods and Feelings Questionnaire at 5 points from 10 to 18 years of age and internalizing behaviors, measured by maternal report of the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire at 7 points from 4 to 16 years of age. RESULTS: Among the 11 181 children included in the analysis (5721 male [51.2%]), the period prevalence of symptoms of depression ranged from 6.0% to 21.6%; for internalizing behaviors, from 10.4% to 16.0%. Although mild to moderate AD was not associated with symptoms of depression, it was associated with internalizing behaviors as early as 4 years of age (mean increased odds of 29%-84% across childhood in adjusted models). Severe AD was associated with symptoms of depression (adjusted odds ratio, 2.38; 95% CI, 1.21-4.72) and internalizing symptoms (adjusted odds ratio, 1.90; 95% CI, 1.14-3.16). Sleep quality mediated some of this association, but it was not explained by differences in sleep duration, asthma/rhinitis, or levels of inflammatory markers (interleukin 6 and C-reactive protein). CONCLUSIONS AND RELEVANCE: Within this population-based birth cohort study in the UK, severe AD was associated with symptoms of depression and internalizing behaviors throughout childhood and adolescence. Risk of internalizing symptoms was increased even for children with mild AD beginning early in childhood, highlighting the importance of behavioral and mental health awareness in this population.