Background: In Israeli colleges and universities, many Arab students experience acculturative stress. Such stress arises from the need to learn new cultural rules, manage the overarching conflict inherent in maintaining elements of their culture of origin (i.e., Arab culture) while incorporating elements of the host culture (i.e., Jewish academic culture), and deal with experiences of prejudice and discrimination present in the host culture. Methods: This study investigated the association between acculturative stress and depressive symptoms among 170 Arab undergraduates from northern and central Israel. It also explored the roles of sense of coherence and coping strategies in the relationship between acculturative stress and depressive symptoms. Participants completed questionnaires on acculturative stress, depressive symptoms, sense of coherence, coping strategies, and demographics. Results: The findings reveal gender differences in the use of different coping strategies and in levels of depressive symptoms. However, academic-year differences were found only in levels of sense of coherence and depressive symptoms. Specifically, female students expressed higher levels of both active and avoidant coping. Moreover, female students and those in their first and second years of university studies reported higher levels of depressive symptoms. Among the male students, acculturative stress was related to depressive symptoms indirectly via sense of coherence and active coping. In contrast, among the female students, acculturative stress was related to depressive symptoms both directly and indirectly via sense of coherence and avoidant coping. Among first- and second-year students, acculturative stress was related to depressive symptoms indirectly via sense of coherence and avoidant coping. However, among third- and fourth-year students, acculturative stress was related to depressive symptoms both directly and indirectly via sense of coherence. Conclusions: This article underscores the significance of gender and academic-year differences in pathways involving acculturative stress.