Objective A growing body of literature suggests that college students display alarming rates of psychological distress. However, studies of responses to significant life stressors in other contexts have found that people respond in heterogeneous ways and that attachment style and ego‐resiliency mitigate the effects of stressors on mental health. Method Individual differences in distress among a cohort of students (N = 157; Mean age = 18.8 years, 62.6% female) across the four years of college were analyzed using latent class growth analysis. Trajectories were then regressed on levels of anxious and avoidant attachment and ego‐resiliency. Results Four discrete patterns emerged characterized by healthy and maladaptive patterns of stress response, indicating that students respond to college in heterogeneous ways. Several patterns showed significant variability in distress by semester. Low levels of anxious but not avoidant attachment predicted membership in the stable‐low distress or resilient class while ego‐resiliency predicted membership in both the resilient and moderate distress classes. Conclusions Findings indicate that low levels of anxious attachment and the ability to flexibly cope with adversity may be associated with better mental health throughout college. Implications from stress response and developmental perspectives are discussed.