Face-to-face and cyberbullying are associated with adverse behavioral or health problems. However, little is known about the association between multiple types of bullying and substance use. The current cross-sectional study compares the association among face-to-face and cyberbullying (bully-only, victim-only, bully/victim, non-involved) and multiple forms of substance use (cigarette use, alcohol use, drunkenness, marijuana use) from a sample of 6th-10th grade students. Data were derived from the 2005-2006 Health Behavior in School-Aged Children study (N = 7189). Zero-inflated Poisson regression analyses of substance use on bullying involvement were conducted, controlling for social-ecological factors. For face-to-face bullying, being bully-only was positively associated with all forms of substance use and being bully/victim was correlated with alcohol use. In the case of cyberbullying, being bully-only and bully/victim increased the incidents of all types of substance use, while being victim-only was only correlated with cigarette and alcohol usage. Further, results indicated that there were some interaction effects of parental monitoring and delinquent friends on the link between face-to-face bullying and substance use. The study findings contribute to scholarship on the linkages among face-to-face bullying, cyberbullying, and substance use within a social-ecological framework which has major implications for school mental health. More specifically, these findings can be useful for school practitioners and health care providers in developing and implementing prevention and intervention programs that address multiple risk behaviors among adolescents.