Research has considered the role of social learning in substance use and determined that social influences are powerful determinants of substance initiation. However, the relationships between peer, sibling, and parent behaviors and e-cigarette initiation among early adolescents, and rural youth in particular, have yet to be examined. The present study investigated how peer delinquency, sibling substance use, and parental approval contribute to risk of e-cigarette initiation across middle school while also examining these associations with alcohol use initiation. Adolescents (N = 663) self-reported perceptions of peer delinquency, sibling substance use, parental approval about substance use, and their own e-cigarette and alcohol use. Multilevel survival analyses were conducted to model the risk of initiation and predictors of this risk. Results indicate that the risk of e-cigarette initiation increased by 75% annually as youths progressed through middle school. All social factors were significant predictors of e-cigarette initiation, while perceived peer delinquency and parental approval predicted alcohol initiation. Results emphasize the importance of early intervention for preventing e-cigarette initiation and the influence of peers and parents on alcohol initiation and the influence of peers, siblings, and parents on e-cigarette use.