In this study, we examine variation across racial and ethnic groups in rates of substance use and age of initiation of use for 15 substances, focusing on a critical neurodevelopmental period for adolescents ages 12 to 18 and young adults ages 19 to 25. Our estimates show that adolescents ages 12 to 18 reported rates of substance use under 3 percent for all substances except for alcohol, tobacco, marijuana, and opioids. Young adults ages 19 to 25 reported higher rates of substance use and much higher rates of alcohol, tobacco, and marijuana use, all above about 30 percent. The rates of substance use for both adolescents and young adults of color were generally lower than or the same as rates for those who are white, except for American Indian or Alaska Native adolescents and adolescents who identify as two or more races, who had higher rates of use. The median age of initiation of substance use, 15, was consistent across racial and ethnic groups and substances, but the age of initiation among those who started using substances earlier differed across racial and ethnic groups. This research suggests prevention and intervention are needed for many groups at ages 11 and earlier; effective, culturally relevant prevention education and early intervention for substance use are needed as early as elementary school. Large-scale, systematic efforts to build the evidence base and support successful community-led models would help support the needs of these young people.