Residential mobility and caregiver social support are two key factors influencing adolescents’ and their caregivers’ health status. However, few studies have examined whether these factors vary across developmental periods. The present study therefore adopted a life course perspective to investigate the longitudinal effects of residential mobility and caregiver social support on a range of individual health outcomes (i.e., caregiver depression, adolescent internalizing problems, and adolescent externalizing problems) among families exposed to disadvantaged social and economic conditions. Data were obtained from the Longitudinal Studies in Child Abuse and Neglect, and 425 children and their caregivers who completed the age 12, 14, 16, and 18 interviews were included in this study. Structural equation modeling was conducted to test the measurement and structural models. The results showed that greater residential mobility was significantly associated with higher levels of caregiver depression, which in turn led to more adolescent internalizing and externalizing problems. Alternatively, higher levels of caregiver social support mitigated the levels of caregiver depression, which in turn resulted in fewer adolescent internalizing and externalizing problems. Highly mobile children and their caregivers were found to be vulnerable to several negative health outcomes and in high need of mental and behavioral health support and services. These findings inform important policy and practice implications on social support for mobile caregivers to address their children’s behavioral problems.