Younger Black men who have sex with men (YBMSM) have the highest rates of HIV incidence in the U.S. and are also exposed to high life stressors (e.g., unemployment, incarceration, and exposure to communality). This study assessed whether life stressors were related to drug use and sexual risk behaviors among a representative sample of YBMSM. The South Side of Chicago and selected adjacent suburbs represents the most populous contiguous Black community in the United States. Over 10% of the estimated YBMSM population in this geographic region were sampled. Major findings indicated that higher life stress was significantly associated with greater odds of transactional sex (aOR=2.19; 95% CI 1.09–4.39), substance use with sex with male and transgender partners (aOR=1.62; 95% CI 1.09–2.39) marijuana (aOR= 2.65; 95% CI 1.43–4.90), crack/cocaine (aOR= 3.21; 95% CI 1.16–8.88) and prescription opioid use (aOR=3.12; 95% CI 1.37–7.13). HIV approaches which focus on environmental stressors and employ a stress and coping framework may support the reduction of drug and sexual risk behaviors among YBMSM. Cognitive and social support approaches might be especially useful in this regard.