This study aimed to articulate the roles of social support and coping strategies in the relation between childhood maltreatment (CM) and subsequent major depressive disorder (MDD) with a comprehensive exploration of potential factors in a longitudinal community-based cohort. Parallel and serial mediation analyses were applied to estimate the direct effect (DE) (from CM to MDD) and indirect effects (from CM to MDD through social support and coping strategies, simultaneously and sequentially). Sociodemographic characteristics and genetic predispositions of MDD were considered in the modeling process. A total of 902 participants were included in the analyses. CM was significantly associated with MDD (DE coefficient (β) = 0.015, 95% confidence interval (CI) = 0.002∼0.028). This relation was partially mediated by social support (indirect β = 0.004, 95% CI = 0.0001∼0.008) and negative coping (indirect β = 0.013, 95% CI = 0.008∼0.020), respectively. Social support, positive coping, and negative coping also influenced each other and collectively mediated the association between CM and MDD. This study provides robust evidence that although CM has a detrimental effect on later-on MDD, social support and coping strategies could be viable solutions to minimize the risk of MDD. Intervention and prevention programs should primarily focus on weakening negative coping strategies, then strengthening social support and positive coping strategies.