Background: Exclusive breastfeeding is the gold standard in infant nutrition. Exclusive breastfeeding has been recognized as an important public health tool for the primary prevention of child morbidity and mortality. The Study Aimed to: Assess the studied mothers’ knowledge and practice regarding exclusive breastfeeding. Design: A descriptive research design was utilized. Setting: This study was conducted at selected maternal and child health centers in Hadayek Helwan and El Sait Khadra in Helwan district. Sample: A purposive sample of 60 mothers and their accompanying infants were attending the previously mentioned settings for BCG immunization during the first week of life and were satisfying the inclusive criteria. Tools: The first toolwas a structured interviewing questionnaire sheet to assess the mothers’ knowledge about exclusive breastfeeding; the second tool was breastfeeding checklist to assess the reported mothers’ practice regarding exclusive breast-feeding. Results: The study findings revealed that nearly two thirds of the studied mothers had unsatisfactory knowledge regarding exclusive breast-feeding and more than three quarters of the studied mothers were incompetent regarding exclusive breast-feeding. Conclusion: The present study concluded that, nearly two thirds of the studied mothers had unsatisfactory knowledge regarding exclusive breast-feeding, more than three quarters of the studied mothers were incompetent regarding exclusive breast-feeding and there was statistically significant difference between total mothers’ knowledge and reported practice regarding exclusive breast-feeding. Recommendations: Periodical health education and awareness programs about the importance of exclusive breast-feeding should be directed for young and primipara mothers.