Young gay, bisexual, and other men who have sex with men (YMSM) are at increased likelihood of experiencing depression and engaging in condomless sexual behaviors. The goal of the current investigation was to examine the relationship between negative mood and compulsive sexual behavior (CSB) and to assess for their individual and combined influence on sexual risk-taking behavior among a diverse sample of YMSM in New York City (the P18 Cohort Study). We first analyzed sociodemographic, depressive symptoms, CSB, and sexual risk-taking from the cross-sectional data of 509, 18- or 19-year-old YMSM recruited using non-probability sampling. We found a significant positive correlation between CSB and depression and between CSB and frequency of condomless anal sex acts reported over the last 30 days. Multivariate results found that the presence of both depression and CSB contributed to elevated sexual risk-taking among these urban YMSM. Clinical implications include the importance of assessing for CSB when depression is present and vice versa in order to improve HIV prevention. Informed by minority stress theory and syndemic theory, our results suggest that interventions focused on the health of YMSM recognize that mental health and social context all interact to increase physical health vulnerability vis-a-vis sexual behaviors, depression, and CSB. Thus, HIV prevention and intervention programs need to incorporate mental health components and services that address these needs.