Objectives: This study investigated the correlation between early exposure to maternal depression (from 1 month to Grade 3) and the body mass index (BMI) and potential for overweight in adolescents at age 15. It further examined if the pathway of this correlation was influenced by psychosocial adjustment during mid-childhood (Grade 3 to Grade 6), specifically through internalizing and externalizing behaviors. Methods: Our study utilized data from 844 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) to assess the effects of maternal depression, observed from when the children were one month old to Grade 3, on BMI and the likelihood of overweight or obesity in adolescents aged 15. We also explored whether the average scores of internalizing and externalizing behaviors between Grades 3 and 6 mediated the impact of early maternal depressive symptoms on subsequent health outcomes. The analysis was adjusted for demographic and socioeconomic factors. Results: Findings revealed that internalizing and externalizing behavioral issues significantly mediated the relationship between prolonged maternal depression exposure and subsequent BMI, as well as the risk of overweight or obesity, in adolescents at age 15. Notably, this mediating effect was predominantly evident in girls. Conclusions: Our research demonstrated that the correlation between prolonged exposure to maternal depressive symptoms in childhood and increased BMI and overweight risk in adolescence was significantly mediated through psychosocial adjustment behaviors. We advocate for further exploration of additional mediating factors in future studies.