Although sex work and younger age increase HIV vulnerability, empirical data regarding the impacts of underage sex work are lacking. We explored associations between features of the risk environment, sex work, and drug use history, and underage sex work entry among 624 female sex workers (FSWs) in Tijuana and Ciudad Juarez, Mexico. Forty-one percent (n = 253) of women began sex work as minors, among whom HIV and any STI/HIV prevalence were 5.2 and 60.7%. Factors independently associated with increased odds of underage sex work were inhalants as the first drug used, forced first injection, number of drug treatment attempts, and recent receptive syringe sharing. Number of recent condom negotiation attempts with steady partners and depression as a reason for first injecting were negatively associated with underage entry. These results underscore the importance of efforts to prevent underage sex work and the wider factors contributing to HIV risk among vulnerable youth and underage FSWs.