Past research has identified parental depression and family-of-origin maltreatment as precursors to adolescent depression and antisocial behavior. Caregiving experiences have also been identified as a factor that may ameliorate or accentuate adolescent psychopathology trajectories. Using the unique attributes of two geographically diverse, yet complementary longitudinal research designs, the present study examined the role of maternal caregiver involvement as a factor that promotes resilience-based trajectories related to depressive symptom and antisocial behaviors among adolescent girls. The first sample comprises a group of US-based adolescent girls in foster care (n = 100; mean age = 11.50 years), all of whom have had a history of childhood maltreatment and removal from the home of their biological parent(s). The second sample comprises a group of UK-based adolescent girls at high familial risk for depression (n = 145; mean age = 11.70 years), with all girls having a biological mother who has experienced recurrent depression. Study analyses examined the role of maternal caregiving on girls’ trajectories of depression and antisocial behavior, while controlling for levels of co-occurring psychopathology at each time point across the study period. Results suggest increasing trajectories of depressive symptoms, controlling for antisocial behavior, for girls at familial risk for depression, but decreasing trajectories for girls in foster care. A similar pattern of results was noted for antisocial behavior trajectories, controlling for depressive symptoms. Maternal caregiver involvement was differentially related to intercept and slope parameters in both samples. Results are discussed with respect to the identification of family level promotive factors aimed at reducing negative developmental trajectories among high-risk youth.