Substance use is prevalent among adolescents, with two-thirds trying alcohol and half trying an illicit drug by twelfth grade (Miech et al., 2015). Substance use is known to affect academic performance. This study utilized nationally representative data from the 2013 Monitoring the Future twelfth grade survey to examine the relationships between substance use, skipping school, grades, and academic engagement. One-quarter of respondents (26%) had never used a substance. The majority (67%) had used at least one substance during the past year. Substance use during their lifetime but not during the past year was uncommon (7%). Lifetime non-users were less likely than past-year users to skip school during the past month and to have low grades. Lifetime non-users also had greater academic self-efficacy and emotional academic engagement relative to past-year users. These findings underscore the importance of screening and intervention for substance use to promote academic achievement and adolescent wellbeing.