Sex exchange is a well-established risk factor for HIV infection. Little is known about how correlates of sex trade differ by biologic sex and whether length of homelessness is associated with sex trade. We conducted a cross-sectional study among a sample of 1,148 homeless and marginally housed individuals in San Francisco to assess correlates of exchanging sex for money or drugs. Key independent variables included length of homelessness; use of crack, heroin or methamphetamine; HIV status; and sexual orientation. Analyses were restricted by biologic sex. In total, 39% of women and 30% of men reported a lifetime history of sex exchange. Methamphetamine use and greater length of homelessness were positively associated with a history of sex trade among women, while heroin use, recent mental health treatment, and homosexual or bisexual orientation were significantly associated with sex trade for men. Crack use was correlated with sex trade for both genders. Correlates of sex trade differ significantly according to biologic sex, and these differences should be considered in the design of effective HIV prevention programs. Our findings highlight the critical need to develop long-term services to improve housing status for homeless women, mental health services for homeless men, and drug treatment services for homeless adults involved in sex work.