Suicide is a significant public health concern and the second leading cause of death for college students. Perceived stress, depression, and mental health stigma are established risk factors for suicidal behavior; however, their interrelationships are unknown. Data were collected from 913 collegiate housing residents (70.8% female; N = 646). Using data from self-report measures, depressive symptoms were examined as a mediator of the relation between stress and suicidal behavior, along with the moderating effect of mental health stigma. Depressive symptoms partially mediated the stress–suicide linkage, and mental health stigma was a significant moderator of the associations between stress and depression, depression and suicidal behavior, and stress and suicidal behavior. Stigmatized attitudes toward mental health treatment, including fear of social repercussion, may exacerbate the deleterious impact of stress on psychopathology and suicide risk. Individual-level therapeutic strategies targeting stress and psychopathology, as well as public health approaches that directly address and attempt to reduce mental health stigma, may reduce suicide risk in college students.