Background: African Americans are disproportionately burdened by substance use consequences and criminal justice system involvement, yet their interrelationship over the life course is not well understood. This study aimed to assess how substance use, crime, and justice system involvement may influence one another from adolescence to midlife. Methods: Data come from a community cohort of urban African Americans first assessed in childhood and followed up into midlife (n = 1242, 606 males, 636 females). We draw on interview data and local, state, and federal criminal records. Participants were assessed at ages 6,16, 32, and 42, with additional record retrieval at age 52. Utilizing structural equation modeling, we estimate pathways between substance use, criminal behavior, and arrests over time by gender.