Running away from home is a known risk factor for commercial sexual exploitation among youth; however, research has not fully investigated the process by which multiple factors at individual, familial, and extra-familial levels increase youths’ risk for runaway behavior. This study applies an ecological risk factor framework to assess risk for runaway behavior among individuals exposed to commercial sexual exploitation and examines mediating relationships between salient risk factors (i.e. substance abuse, insufficient basic needs, having a much older boyfriend/girlfriend) and runaway behavior. A cross-sectional, retrospective survey was administered to individuals involved in the commercial sex industry using Respondent Driven Sampling methods (N = 273). Bivariate results suggested associations between runaway behavior and childhood emotional and physical abuse, having friends who sold sex, having a much older boyfriend/girlfriend, dropping out of school, being worried about where to eat/sleep, homelessness, and frequent alcohol and drug use prior to entering the commercial sex industry. Hierarchical logistic regression revealed that individuals with runaway behavior histories were more likely to have frequently used alcohol and/or drugs and to have insufficient basic needs compared to those did not run away; however, these factors were no longer significant after accounting for having a much older boyfriend/girlfriend. Having an older boyfriend/girlfriend fully mediated the relationship between frequent alcohol and/or drug use and runaway behavior. Findings support the need for community and school-based prevention programs that target these risk factors with a specific focus on healthy dating relationships, which may reduce risk for runaway behavior and subsequent commercial sexual exploitation