Adverse and advantageous childhood experiences (ACEs and counter-ACEs) during adolescence are understudied. This study examined how childhood experiences affect youth tobacco/alcohol use. Participants included 489 U.S. adolescents (baseline 10–13 years; 51% female) from the first five waves of the Flourishing Families Project. Results of the cross-lagged model showed ACEs were predictive of early tobacco use only. Counter-ACEs in wave two and wave three predicted, respectively, decreased tobacco and decreased alcohol use in the following wave. Counter-ACEs were also correlated with reduced alcohol and tobacco use in later waves. These findings indicate the salience of counter-ACEs over ACEs in persistent and late adolescent substance use, though ACEs may be important to consider to prevent very early initiation of tobacco.