This prospective longitudinal study investigated depressive symptoms and its association with students' demographic, academic, and health factors in undergraduate students of pharmacy in Syria. Students attending any year (1st to 5th year) were assessed in the first semester (time 1) and in the second semester (time 2). An academic year comprises two semesters of 16 weeks each. Data for 450 students were analyzed at time 1, and 262 students were assessed at the two time points. Our results showed that most of the students experienced depressive symptoms, with a substantial percentage presenting moderate to severe levels of symptoms (35% or 450 students at time 1; 23% or 262 students at time 2). Across the two semesters, a significant decrease in depressive symptoms was observed for students with complete data at the two time points. Depressive symptoms at time 2 increased significantly with increasing depressive scores at time 1 and decreasing students' expectations about their academic performance. Our results support the clear need for dynamic, full-time, and accessible psychological services at the university to promote and assess mental health and to deliver psychological interventions to students at need.