Although lesbian, gay, and bisexual (LGB) youth with a history of homelessness (running away or being evicted from their homes by parents) report more psychological symptoms than homeless heterosexual peers, it is unclear whether symptoms are due to homelessness, given the absence of a non-homeless comparison group. This study longitudinally investigates whether LGB youth with a history of homelessness report more subsequent psychological symptoms than non-homeless LGB youth and examines potential mediators of any such relationships. Of the 156 LGB youth interviewed (49% female; 78% non-White), 48% reported past homeless experiences. Homelessness was associated with subsequent symptoms of anxiety, depression, conduct problems, and substance abuse and to changes in symptoms over time even after controlling for childhood sexual abuse and early development of sexual orientation. Stressful life events, negative social relationships, and social support from friends mediated the relationships between homelessness and symptomatology. These findings suggest the need for interventions to reduce stress and enhance social support among LGB youth with a history of homelessness in order to reduce psychological symptoms.