The perinatal period is crucial for both mother and newborn, and mental health, including prenatal and postpartum depression (PPD), is a significant aspect. Screening for these disorders allows for early treatment and helps prevent risks to both mother and child. This prospective cohort study was carried out at University Hospital Obstetrics in Damascus City. The first phase was during the third trimester of pregnancy and the second phase involved a follow-up assessment after 6 weeks of delivery. The Arabic-validated version of the Edinburgh Postnatal Depression Scale questionnaire (EPDS) was used. A cutoff of 13 or higher was used to determine the presence of probable depression in both assessments. Of 347 pregnant women, 38.6% had prenatal depression (PND). 295 patients have achieved the second assessment, of which 30.2% had PPD. Furthermore, 42.6% who had PND developed PPD on follow-up. Binary logistic regression indicated that PND was predicted by non-Syrian nationality, paternal absence, poor financial status, number of previous pregnancies, and a history of depression independent of pregnancy. PPD was predicted by a history of PPD, and work status. Findings underscore potential value of early screening for depressive symptoms as a predictive measure. It is recommended that women with a history of depression receive heightened attention and care, irrespective of the timing of their depressive episodes.