Although perceived discrimination is linked to poor mental health, little is known about the mental health significance of the number of perceived reasons for discrimination. Using survey data from a communitybased sample of adults living in Miami, Florida (n = 1,944), this study tests whether those reporting multiple perceived reasons for major discriminating events are at increased risk for depression. Cross-sectional and longitudinal analyses reveal those reporting multiple reasons for major discrimination are at increased risk for lifetime major depression and subsequent depressive symptoms. While social support and mastery partially mediated the link between multiple perceived reasons for discrimination and subsequent depressive symptoms, this psychological risk was not fully explained by these coping resources. Together the findings underscore the psychological toxicity of perceived discrimination and the importance of considering multiple perceived reasons for discrimination as a risk factor for poor mental health.