Post-partum depression (PPD), a major health concern, has harmful consequences on mothers, their children, and families. This study aimed to assess the prevalence of postpartum depression among mothers having children under 2 years old in Beni-Suef City and its relation to breastfeeding. This study was an analytical cross-sectional study conducted over nine months, from March to November 2021. Data were collected from 380 mothers attending a health service in any of the 4 health care facilities, which were randomly selected from the total number of healthcare offices and units in Beni-Suef city: (El-Kom El-Ahmar, Sherif Basha health care centers, El Ghamrawy and Sharq El-Nile health offices). Data were collected using a self-structured questionnaire prepared in Arabic and the validated Arabic version of the Edinburgh Postnatal Depression Scale questionnaire for screening of PPD. The prevalence of PPD among participants was 70.3%. There was a significant relationship between the high probability of PPD and being a working mother, having ≤ 2 children, having both gender of children, cesarean section labor, delayed initiation of breastfeeding after 1st hour, and presence of breast pain during breastfeeding.