Objective: Prospective research is needed to better-understand changes in substance use from before to during the coronavirus disease (COVID-19) pandemic, among emerging adults (18–25 years), a high-risk group for substance use. Method: N = 1,096 (weighted sample N = 1,080; 54% female) participants enrolled in the Québec Longitudinal Study of Child Development, who completed prepandemic (2019; 21 years) and COVID-19 (mid-March to mid-June 2020) surveys. COVID-19-related and preexisting factors were examined as moderators of change in substance use. Results: Full sample analyses revealed decreased binge drinking (p f² = 0.02), but no changes in alcohol and cannabis use. Stratified analyses revealed emerging adults who reported p150, f² = 0.05) and binge drinking (p f² = 0.01), but not their cannabis use. Conversely, emerging adults who reported >monthly use prepandemic decreased their binge drinking (p150, f² = .12) and cannabis use (p150, f² = .06), but did not change their alcohol use frequency. Several factors moderated change in substance use, including employment loss (p = .005, BF > 39, f² = .03) and loneliness (p = .018, BF > 150, f² = .10) during COVID-19. Conclusions: Changes in alcohol and cannabis use frequency among emerging adults in the first 3 months of COVID-19 largely differed according to prepandemic substance use, COVID-19-related factors, and preexisting factors. While some youth with preexisting vulnerabilities (e.g., more frequent substance use prepandemic) remained stable or decreased their substance use during COVID-19, emerging adults who experienced employment loss, loneliness, and financial concerns during COVID-19 increased their substance use, highlighting the need for increased supports for vulnerable populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved)