This 10-year study followed 134 caregivers of young adults with autism and intellectual disability, examining the effects of caregivers' coping strategies, sociodemographic features, and young adult symptomatology on caregiver well-being and depression. Lower caregiver education and higher young adult externalizing behaviors predicted lower well-being and higher depression among caregivers. Caregivers who were Black or mixed-race experienced higher depression than White caregivers. All five coping strategies investigated predicted changes in caregiver well-being and/or depression, with some effects moderated by young adult externalizing behaviors and sociodemographic features. Notably, higher use of positive coping among caregivers of adults with high externalizing behaviors predicted higher caregiver well-being and lower depression. Findings highlight the importance of effective coping strategies for improving caregiver mental health.