Objective: Supportive social relationships can have direct positive effects on health and mitigate the negative impact of stressors. This study investigated the main effect of perceived social support on STI/HIV risk and prevention behaviors. The buffering effect of perceived social support on the impact of proximal minority stressors, like internalized homonegativity, was also examined on one risk behavior specifically, condomless anal sex (CAS) without HIV pre-exposure prophylaxis (PrEP) use. Methods: HIV-negative gay, bisexual, and other men who have sex with men (GBM) were recruited using respondent driven sampling from three major Canadian urban centers (n = 1,409). GBM completed measures of perceived social support, proximal minority stress, and engagement in STI/HIV risk and prevention behaviors. Results: Higher perceived social support was positively associated with a several health behaviors, including recent STI and HIV testing, discussing HIV status with prospective partners, the use of behavioral HIV-risk reduction strategies during sexual encounters, and a lower likelihood of engaging in CAS without PrEP. There was evidence of moderation as well. Among GBM with higher perceived social support, internalized homonegativity was no longer associated with increased odds of engaging in CAS without PrEP. Conclusions: The results of the current study advance social support theory to GBM in the context of biomedical prevention, showing both evidence of both direct associations and buffering effects on STI/HIV risk and prevention behaviors. This highlights the importance of promoting social support seeking in interventions aimed at improving GBM health.