Background: Substance use among Black sexual minority men (BSMM) is a significant public health focus of prevention interventions due to its association with sexual risk behaviors and transmission of HIV. Traumatic experiences and mental health challenges may interact to create a syndemic associated with substance use in this population; this may be moderated by social support however. Methods: Using a multicenter prospective cohort of 1068 BSMM, we conducted a longitudinal syndemic latent transition analysis testing whether baseline and 6-month race and sexuality-targeted violence, intimate partner violence, other traumatic experiences, depression, and internalized homophobia was associated with 12-month substance use. We also tested if social support modified this and was associated with transitions between statuses. Results: Our analysis identified four statuses: A "low-risk" status characterized by the lowest proportions of syndemic factors, and 3 "high-risk" statuses, characterized by higher proportions of syndemic factors. All three high-risk statuses were associated with higher substance use than the low-risk status, with the greatest association observed with "high-risk status C" (aRR = 4.54, 95 % CI 1.98, 10.40). Social support attenuated this association (Interaction aRR = 0.21, 95 % CI 0.05, 0.85) and was associated with lower transition rates from low to high-risk status 6 months later (Transition ratio = 0.45, 95 % CI 0.29, 0.69). Conclusions: Our findings identified a syndemic of trauma, depression, and homophobia among BSMM associated with substance use, but attenuated by social support. Future research into the role of social support and resiliency in substance use prevention and recovery is recommended.