Objectives: To prospectively investigate associations between overweight and depressive symptoms in Asian and Hispanic adolescents. Methods: Data included 780 Hispanic and 375 Asian students. Structural equation model was used to prospectively explore moderation effects of gender, ethnicity, and acculturation on associations of overweight, body image dissatisfaction, and depressive symptoms. Results: Significant mediation effect was found only in Asian girls (mediation effect = 0.16, P less than 0.05) and girls with high acculturation (mediation effect = 0.17, P less than 0.05). Overweight significantly predicted higher body image dissatisfaction, which in turn was significantly related to depressive symptoms. Conclusion: Our findings help understanding the association of overweight and experience of depressive symptoms.