PurposeEvaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive Development Study. MethodsIn 2018–2019, 9,270 youth aged 11.5–13.0 completed a prepandemic assessment of past-month alcohol and drug use, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same-age youth across these eight timepoints. ResultsPandemic-related decreases in the past-month prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% prepandemic, p <.001). Pandemic-related increases in inhalant use (p = .04) and prescription drug misuse (p < .001) were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021(0.1%-0.2% vs. 0% pre-pandemic). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from prepandemic levels in May 2021 (0.5% vs. 0.2% prepandemic, p = .09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families. DiscussionAmong youth ages 11.5–13.0 years old, rates of alcohol use remained dramatically reduced in May 2021 relative to prepandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite the partial restoration of prepandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use.