Young men who have sex with men (YMSM) report higher rates of substance use than their heterosexual peers and minority stress has been posited as a risk factor for substance use. The associations between specific types of minority stress and substance use have been inconsistent throughout the literature and few studies have examined mechanisms underlying these associations. Drawing on minority stress theory and the motivational model of alcohol use, we propose that one mechanism underlying these associations may be people’s motivations for using substances, including using substances to cope with negative emotions and to enhance pleasure. The goals of the current study were: (a) to examine the associations among minority stressors, substance use motives, and substance use problems, and (b) to examine substance use motives as mediators of the associations between minority stressors and substance use problems. Baseline self-report data were used from a cohort of 370 YMSM enrolled in a larger study of substance use and sexual behavior. Results indicated that using marijuana to cope mediated the association between victimization and marijuana use problems. Using other drugs to cope mediated the associations between victimization and drug use problems and between internalized stigma and drug use problems. Drinking to cope and to enhance pleasure mediated the association between internalized stigma and alcohol use problems. In sum, substance use motives, especially using substances to cope, act as mechanisms through which certain types of minority stress influence substance use problems among YMSM.