Adolescent substance misuse is a persistent concern in the USA and student substance possession on campus presents as an increasing challenge for administrators. This study seeks to understand how students are differentially disciplined for substance possession based on substance type and student race/ethnicity in US schools. Based a national sample of 99,181 students (Grades 6 through 12) from 3285 schools across school years 2012-13 to 2018-19, we used descriptive analysis to explore how students possessing alcohol, tobacco, or drugs on campus on their first referral were disciplined. Using multi-level logistic modeling, we assessed to what extent use of exclusionary discipline (i.e., out-of-school suspension [OSS], in-school suspension [ISS]) varied by year, substance type, and student race/ethnicity (i.e., White/Caucasian, African American/Black, Hispanic/Latino/a/e). Descriptive results indicate that management of substance possession in schools relies heavily on exclusion over other actions. Results from multi-level models for OSS and ISS demonstrated shifts in use of each action over time, significantly different rates by substance type possessed, and a significant student race/ethnicity by substance interaction. Findings suggest that alternative approaches to exclusion for substance possession have not been widely implemented; however, the use of exclusion may be shifting from OSS to the use of ISS for these students. Suggestions for coherent, preventive programming for substance misuse and for planning alternative, supportive responses are reviewed.