There is an extensive literature describing the detrimental effects of adverse childhood experiences (ACE; e.g., abuse, neglect, and household dysfunction) on physical and mental health. However, few large-scale studies have explored these associations longitudinally in urban minority cohorts or assessed links to broader measures of well-being such as educational attainment, occupation, and crime. Although adversity and resilience have long been of interest in developmental psychology, protective and promotive factors have been understudied in the ACE literature. This paper investigates the psychosocial processes through which ACEs contribute to outcomes, in addition to exploring ways to promote resilience to ACEs in vulnerable populations. Follow-up data were analyzed for 87% of the original 1,539 participants in the Chicago Longitudinal Study (N = 1,341), a prospective investigation of the impact of an Early Childhood Education program and early experiences on life-course well-being. Findings suggest that ACEs impact well-being in low-socioeconomic status participants above and beyond the effects of demographic risk and poverty, and point to possible mechanisms of transmission of ACE effects. Results also identify key areas across the ecological system that may promote resilience to ACEs, and speak to the need to continue to support underserved communities in active ways.