Objective: The aim of this study was to assess mothers' knowledge on newborn care as well as factors associated with poor knowledge. Methods: The study setting was two maternity hospitals, one urban and other rural, which were randomly selected from the maternity hospitals in Alexandria and El Behera governorates. A convenience sample of 422 mothers of newborns was selected from the previously mentioned settings. A structured interview questionnaire was designed and utilized by the researchers to collect the data. Maternal knowledge on newborn care was assessed and a knowledge score was created by allocating 1 point for each correct response. Knowledge score was classified as 'good', 'satisfactory' and 'poor' scores. Results: The study results showed that 59.5% of mothers had either satisfactory or good overall knowledge. More than half of the mothers (55.7%) demonstrated a poor knowledge about some breastfeeding practices, mainly on initiation of breastfeeding (43.7%), proper attitude towards hypogalactia (42.7%), giving pre-lacteal feeds (38.4%), non-timed lactation (19.9%) and only 17.7% correctly identified the duration of exclusive breastfeeding. Mothers demonstrated satisfactory and good knowledge about the newborn warning signs (67.8%), with more than 70% of mothers recognizing 8 of 9 symptoms and/or signs that needed the urgent attention of a healthcare provider. According to multivariate analysis, rural women (odds ratio (OR)= 1.62; 95% CI 1.43-2.12),primiparae (OR= 1.77; 95% CI 1.53-2.72), mothers with lower family monthly income (OR=2.04; 95% CI 1.33-3.32) and those who never attended schools (OR=2.00; 95% CI 1.28-3.11) were more likely to have poor knowledge. Conclusion: Mothers had satisfactory orgood levels of knowledge about care of the umbilical cord and recognition of dangerous signs, but knowledge about breastfeeding was poor. Maternal education programs should place more emphasis on first-time mothers and those having lower socio-economic level as evident by lower monthly family income and lack of education.