Alcohol misuse and depression are highly comorbid. Self-medication theory posits that depressed individuals use alcohol to reduce negative emotions. Research suggests that the co-pattern of depression and alcohol misuse is not uniform, and that emerging adults transitioning out of university can be differentiated into subgroups based on their co-patterns. We aimed to replicate and extend this study with emerging adults during university by examining whether baseline individual differences predicted subgroup membership. Undergraduates (N = 300) completed four waves of self-reports at 6-month intervals over 18-months. Parallel process latent class growth modeling supported three classes: Class 1, the “high-risk comorbid” group, had high stable depression and high stable alcohol misuse (n = 28). Class 2, the “moderate-risk depression-only group” had high stable depression but low decreasing alcohol misuse (n = 87). Class 3, the “low-risk normative” group, had low stable depression and low decreasing alcohol misuse (n = 185). Multinomial regressions showed that male sex, higher hopelessness, impulsivity, and anxiety sensitivity, and higher coping-with-depression and enhancement drinking motives, differentiated Class 1 from Class 3. Higher impulsivity and lower hopelessness, and higher enhancement motives, differentiated Class 1 from Class 2. Higher hopelessness, and higher coping-with-depression and conformity motives, differentiated Class 2 from Class 3. We utilized a subclinical sample and a short follow-up period. Emerging adults display differing co-patterns of depression and alcohol misuse over time during university, including both high-, moderate-, and low-risk subgroups. Our results provide novel evidence subgroups that can be distinguished based on sex, drinking motives, and personality.