Suicide is the second leading cause of death in college students, making it a significant public health concern on college campuses. Perceived stress, depression, and mental health stigma are established risk factors for engaging in suicidal behaviors; however, their interrelationships are unknown. In a sample of 913 college students, we examined the role of depressive symptoms as a potential mediator of the relation between stress and suicidal behavior, and mental health stigma as a moderator of that effect. In bivariate analyses, perceived stress, depressive symptoms, mental health stigma and suicidal behaviors were all positively correlated. Additionally, depressive symptoms partially mediated the relation between stress and suicidal behaviors, such that greater stress was related to more depression and, in turn, to greater engagement in suicidal behavior. Further, mental health stigma significantly moderated this mediating effect, exacerbating the deleterious relations between perceived stress and depression, stress and suicidal behavior, and between depression and suicidal behaviors. Negative, unaccepting attitudes toward mental health treatment, such as fear of social repercussion, may contribute to a worsening of symptoms and suicide risk in students experiencing distress. Our findings may have clinical and public health implications. At the individual level, addressing stress and depression, perhaps by bolstering coping efficacy via Cognitive Behavioral Therapy and, at the community level, implementing strategies to reduce mental health stigma, perhaps via awareness messaging campaigns, may reduce risk for suicide.