Although overdose deaths in the US have increased exponentially for the past four decades, these shifts have historically affected adults, while pediatric overdose rates remained stable. However, this may be changing, given that the illicit drug supply has become increasingly hazardous in recent years, as illicitly-manufactured-fentanyls (IMFs) and other synthetic opioid and benzodiazepine analogues are increasingly sold as heroin and counterfeit prescription pills. We calculated drug overdose deaths per 100,000 population by 5-year age groups for the 2010-2021 period. For high-school-aged adolescents (age 14-18), we stratified rates by race/ethnicity, census region, associated substance, and ICD-10 cause-of-death intent categories. Adolescent overdose mortality saw a sharp increase between 2019 and 2020, from 2.35 per 100,000 to 4.58 per 100,000, representing a 94.3% increase, the largest percent increase of any 5-year age group. American Indian or Alaska Native (AIAN) adolescents, Latinx adolescents, and adolescents in the West census region were disproportionately affected, overdose death rates 2.15, 1.31, and 1.68 times the national average in 2021, respectively. Trends were driven by fatalities involving IMFs, which nearly tripled from 2019 to 2020, and represented 76.6% of adolescent overdose deaths in 2021. Sharp increases in adolescent drug overdose deaths, despite flat or declining drug use rates, and no increase in deaths from alcohol or most drugs, reinforce that rising fatalities are likely driven by an increasingly toxic, IMF-contaminated drug supply. Rising racial disparities in overdose require a prevention approach that ameliorates deep-seated social and economic inequalities as well as poor access to mental and physical healthcare and social services for AIAN and Latinx adolescents. Our results should also be understood in the context of rising rates of adolescent mental illness during the COVID-19 pandemic. These findings highlight the urgent need for accurate, harm-reduction-oriented education for early adolescents about the risks of an evolving drug supply, as well as greater access to naloxone and services that check drugs for the presence of IMFs.