We assessed whether perceived discrimination predicted changes in psychological distress and substance use over time and whether psychological distress and substance use predicted change in perceived discrimination over time. We also assessed whether associations between these constructs varied by gender. Our sample included 607 Black emerging adults (53% female) followed for 4 years. Participants reported the frequency with which they had experienced racial hassles during the past year, symptoms of anxiety and depression during the past week, and cigarette and alcohol use during the past 30 days. We estimated a series of latent growth models to test our study hypotheses. We found that the intercept of perceived discrimination predicted the linear slopes of anxiety symptoms, depressive symptoms, and alcohol use. We did not find any associations between the intercept factors of our mental health or substance use variables and the perceived discrimination linear slope factor. We found limited differences across paths by gender. Our findings suggest a temporal ordering in the associations among perceived racial discrimination, psychological distress, and alcohol use over time among emerging adults. Further, our findings suggest that perceived racial discrimination may be similarly harmful among men and women.