BACKGROUND: Lesbian, gay, bisexual, transgender, queer and questioning (LGBTQ) youth are overrepresented in foster care and report greater substance use during adolescence. OBJECTIVE: Using an intersectional lens, the current study investigates differences in foster care placement and variation in substance use at the intersections of foster care and sexual orientation, gender identity, racial/ethnic identities, and sex assigned at birth. PARTICIPANTS AND SETTINGS: A sample of 121,910 LGBTQ youth (grades 6-12) completed either the Minnesota Student Survey in 2019, the California Healthy Kids Survey from 2017 to 2019, or the 2017 LGBTQ National Teen Study. METHODS: Youth reported their substance use in the past 30 days (alcohol, binge drinking, cigarette, marijuana), social positions (sexual orientation, gender identity, racial/ethnic identities, sex assigned at birth), living arrangement (foster care or not), and grade in school. Logistic regression was used to examine the main and interaction effects of foster care and social positions on youth substance use. RESULTS: Results indicated significant differences in substance use at the intersection of foster care placement and youth social positions. Significant two-way interactions for foster care placement and social positions emerged predicting alcohol, binge drinking, and marijuana use. CONCLUSIONS: Findings show that LGBTQ youth in foster care are at higher risk for substance use than those not in foster care. Particular support is needed for lesbian, gay, and questioning youth, transgender youth, LGBTQ youth assigned male at birth, and Asian or Pacific Islander LGBTQ youth in foster care.