PurposePrevention efforts are critical to avoid the negative consequences of substance use in adolescents. This study aimed to examine national trends and sociodemographic differences in adolescents' participation in school-based substance use prevention (SUP) education, community-based SUP programs, as well as family conversations about substance use. MethodsPublicly available data for adolescents aged 12–17 from the annual cross-sectional surveys of the National Survey on Drug Use and Health 2011–2019 were analyzed. ResultsAcross the survey years, up to 74.9%, 12.2%, and 58.1% of adolescents reported having participated in school-based SUP education, community-based SUP programs, and family conversations about the danger of substance use in the past-year, respectively. From 2011 to 2019, statistically significant decreases were observed in adolescents' participation in school-based SUP education (OR = 0.97, 95% CI: 0.96, 0.98, p < 0.001) and community-based SUP programs (OR = 0.98, 95% CI: 0.97, 0.99, p < 0.001). Meanwhile, no significant changes were observed in adolescents' participation in family conversations about the dangers of substance use. Overall, lower levels of participation in school-based and community-based SUP programs were found in adolescents aged 16–17. Adolescents living in rural areas showed lower levels of participation in school-based SUP programs and family conversations about SUP. Racial/ethnic minority adolescents overall were less likely to participate in conversations with parents about SUP than Whites. ConclusionsFurther development and implementation of developmentally appropriate, gender-specific, culturally sensitive, and contextually informed SUP programs at school, community, and family levels are needed.