The relationship between adverse childhood experiences (ACEs) and frequent substance use (SU) is not well understood, impeding prevention efforts. We assessed the relationship between ACEs and frequent SU and investigated if different modalities of physical activity (PA) moderate this pathway. The analysis included persons enrolled in the National Longitudinal Study of Adolescent to Adult Health who responded to surveys at Waves I (11-20 years), III (18-27 years), and IV (24-33 years). The impacts of cumulative ACEs and PA modalities on daily cigarette smoking, daily cannabis use, and binge drinking ≥ 3 times a week in emerging and early adulthood were assessed through adjusted logistic regression models. Among the sample (N=9451), 29.3%, 12.5%, and 7.8% experienced 1, 2, or 3 or more ACEs, respectively. With exception to binge drinking, cumulative ACEs (3+) were strongly associated with daily cannabis use in Wave III (aOR: 2.5; 95% CI: 1.6-3.6) and Wave IV (aOR: 2.1; 95% CI:1.3-3.3) and daily cigarette smoking in Wave III (aOR: 2.4; 95% CI: 1.9-3.0) and Wave IV (aOR: 2.3; 95% CI: 1.8-2.8). No PA modality moderated the ACEs to SU pathway; however, walking for exercise lowered the odds of current and prospective daily cannabis and cigarette use by 20-40%. Strength training, team sports, and individual sport participation were associated with 20-30% reduced risks of future daily cigarette use. The impacts of ACEs exposure on frequent SU persist into emerging and early adulthood. Future research should investigate the potential of PA to improve SU prevention strategies.< Réduire