Research on COVID-19's effect on substance use is mixed, and few studies have focused on adolescents. We assessed whether implementation of the COVID-19 lockdown affected substance use and changed perceptions of psychoactive substance availability in middle and high school students. We assessed self-reported use and perceived availability of alcohol, tobacco cigarettes, electronic cigarettes, marijuana, synthetic marijuana, nonprescribed prescription drugs, and illicit drugs (heroin, inhalants) among middle and high school respondents aged 11-18 years to the Rhode Island Student Survey (N = 17 751). An administrative pause because of COVID-19 lockdowns allowed us to divide results into surveys completed before (January through March 2020; n = 13 259) and after (November 2020 through May 2021; n = 4492) the lockdown implementation. We determined the effects of the COVID-19 lockdown using logistic regression models, adjusting for age, gender/sexual orientation, middle/high school level, and city/town classification. After the COVID-19 lockdown implementation, the odds of respondents using psychoactive substances decreased, with the largest decreases occurring for prescription drugs (odds ratio [OR] = 0.39; 95% CI, 0.28-0.54) and inhalants (OR = 0.37; 95% CI, 0.26-0.53). The odds of respondents perceiving difficulties in obtaining psychoactive substances significantly increased after lockdown implementation, with the largest increases occurring for prescription drugs (OR = 1.53; 95% CI, 1.39-1.69) and illicit drugs (OR = 1.65; 95% CI, 1.44-1.88). COVID-19 lockdown implementation was associated with a decreased perception of availability of psychoactive substances and use of psychoactive substances. Decreases in substance use may be because of decreased perceived availability and increased parental support and oversight. Interventions that focus on parental oversight and strengthened policies to disrupt the licit and illicit drug markets are needed.