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Appearance-related teasing is a pervasive form of bullying during adolescence. Yet, the impact of appearance-related teasing on risk for alcohol and marijuana use is unknown. This study, therefore, examined the relationship between appearance-related teasing and the use of alcohol and marijuana in a sample of 1,344 students (52% female; 51% non-Hispanic White; ages 11–14 years, M = 13.20, SD = 0.65) from 5 public middle schools. Participants completed a survey that assessed demographic characteristics, weight status, depressive symptoms, general peer victimization, experiences of appearance-related teasing perpetrated by family and peers, and substance use in the fall of 2016 (Time 1 [T1]) and spring of 2017 (T2). Findings at baseline (T1) indicated that more frequent appearance-related teasing was associated with higher concurrent levels of total alcohol consumption, binge drinking, and marijuana use (ps < .001). Longitudinally, more frequent appearance-related teasing at T1 predicted greater increases in total alcohol consumption (p < .01) and binge drinking frequency (p < .05) by T2 but was unrelated to changes in marijuana use (p > .05), adjusting for age, gender, race and ethnicity, perceived socioeconomic status, body mass index z scores, depressive symptoms, general peer victimization frequency, and substance use at T1. Moderation analyses generally suggested that the positive associations between appearance-related teasing and alcohol use measures were stronger among adolescents who were girls (vs. boys) and who were overweight or obese (vs. nonoverweight). These findings suggest that appearance-related teasing may play a role in the origins of alcohol use during early adolescence and emphasize the need to mitigate the effects of appearance-related teasing and prevent early substance use.