Background: Postpartum depression (PPD) affects around 10% of women, or 1 in 7 women, after giving birth. Undiagnosed PPD was observed among 50% of mothers. PPD has an unfavorable relationship with women’s functioning, marital and personal relationships, the quality of the mother-infant connection, and the social, behavioral, and cognitive development of children. We aim to determine the frequency of PPD and explore associated determinants or predictors (demographic, obstetric, infant-related, and psychosocial factors) and coping strategies from June to August 2023 in six countries. Methods: An analytical cross-sectional study included a total of 674 mothers who visited primary health care centers (PHCs) in Egypt, Yemen, Iraq, India, Ghana, and Syria. They were asked to complete self-administered assessments using the Edinburgh Postnatal Depression Scale (EPDS). The data underwent logistic regression analysis using SPSS- IBM 27 to list potential factors that could predict PPD. Results: The overall frequency of PPD in the total sample was 92(13.6%). It ranged from 2.3% in Syria to 26% in Ghana. Only 42 (6.2%) were diagnosed. Multiple logistic regression analysis revealed there were significant predictors of PPD. These factors included having unhealthy baby adjusted odds ratio (aOR) of 11.685, 95% CI: 1.405–97.139, p = 0.023), having a precious baby (aOR 7.717, 95% CI: 1.822–32.689, p = 0.006), who don’t receive support (aOR 9.784, 95% CI: 5.373–17.816, p = 0.001), and those who are suffering from PPD. However, being married and comfortable discussing mental health with family relatives are significant protective factors (aOR = 0.141 (95% CI: 0.04–0.494; p = 0.002) and (aOR = 0.369, 95% CI: 0.146–0.933, p = 0.035), respectively. Conclusion: The frequency of PPD among the mothers varied significantly across different countries. PPD has many protective and potential factors. We recommend further research and screenings of PPD for all mothers to promote the well-being of the mothers and create a favorable environment for the newborn and all family members.