This study examined associations of intragroup marginalization and cultural incongruity with acculturative stress and depressive symptoms among 155 undergraduate U.S. college students of Mexican heritage. Findings indicate that perceived interpersonal distancing by the family (intragroup marginalization) and perceived lack of cultural fit between the respondent and academic institution (cultural incongruity) had statistically significant direct and indirect effects on depressive symptoms via acculturative stress. Results also show that 39.7% of the variance corresponding with depressive symptoms was accounted for by intragroup marginalization, cultural incongruity, acculturative stress, and other exogenous variables.