Each year, thousands of female adolescents run away from home due to sexual abuse, yet they continue to be victims of sexual assault once on the street. To date, few studies have examined how various forms of victimization are related to different types of substance use. The purpose of this article is to investigate the relationship between street exposure, childhood abuse, and different forms of street victimization with alcohol and marijuana use among 137 homeless and runaway female adolescents. Results from path analysis revealed that child sexual abuse was positively linked to trading sex and sexual and physical victimization. In addition, those who have traded sex experienced greater physical victimization, and who have spent more time away from home, used alcohol more frequently. Moreover, trading sex and experiencing more types of sexual victimization were positively linked to more frequent marijuana usage. Age, age at first run, longest time away from home, sexual abuse, and trading sex had significant indirect effects on alcohol and/or marijuana use. Together, these factors accounted for 27% of the variance in alcohol use and 37% of the variance in marijuana use.