Background: Postpartum depression (PPD) is a common mood disorder affecting about 10–15% of adult mothers annually. This study aimed to find the prevalence and associated factors of postpartum depression among women in Herat province in Afghanistan. Methods: Across-sectional study was conducted between 11 July 2021 and 15 September 15, 2021, among women who delivered a baby at Rezaie Maternal Hospital of Herat province (Afghanistan). A total of 242 women participated in the first phase of this study with a mean age of 25.40 ± 5.510. To assess the depression among participants, the Edinburg Postnatal Depression Scale was used. Results: Almost half the participants reported that it was their first labour (45.0%). In the first phase, nearly half of the participants were found to have depression (45.5%). In the second phase of this study, less than one in three participants had depression (30.7%). More than one in five participants changed from depression to normal (21.5%). Almost half of the participants remained the same in both phases of this study (47.8%). Conclusion: It is crucial to examine women's psychological health during the postnatal period to understand how we may assist women through targeted interventions based on their particular needs. Our study shows that the post-partum depression among women in Herat province of Afghanistan, decreases and factors such as educational level, number of family members, happening of bad event during the past month, and presence of physical illness have a direct impact on postpartum depression.