Victims of child sex trafficking in prostitution in the United States are often overlooked, misidentified, and among the most underserved type of child victim of crime. The majority of previous research on child sex trafficking has been conducted without a theoretical framework or reliable sampling methods. In this study, a schematic composed of a series of stepping-stones from childhood abuse to prostitution, which has been described by gendered pathways researchers, served as a sensitizing template for the study's development of a strain-reactive pathway into child sex trafficking. Agnew's general strain theory provided the primary theoretical basis for the proposed pathway, supplying both explanations of the generative factors of the pathway and the mechanisms operating within the life trajectory terminating in child sex trafficking in prostitution. Based on this theoretical framework, this study utilized structural equation modeling to examine the pathway by investigating the effects of caregiver strain, child maltreatment, and risk-inflating responses to strain on vulnerability to victimization in child sex trafficking in prostitution. Four structural equation models, incorporating different forms of child maltreatment, were assessed using data from a matched sample of 174 minority females who were residents of one U.S. city and participated in a longitudinal study on the effects of child sexual abuse. Findings show that the occurrence of child maltreatment including child neglect, child physical abuse, and juvenile sexual victimization increased with caregiver strain. Consequentially, neglected and abused children were more likely to have engaged in the risk-inflating responses of running away and earlier initiation of drug or alcohol use, and they also reported higher levels of relational shame. Both running away and early initiation of substance use impacted vulnerability to victimization in child sex trafficking in prostitution. Lastly, implications of the findings related to protection and intervention strategies that are projected to obstruct the progression of minors along the analytically identified pathway into child sex trafficking in prostitution are presented for criminal justice professionals, child protection investigators, and social service providers.