The overall objective of this study was to determine factors influencing the knowledge and practice of Exclusive Breast Feeding1 (EBF) among lactating mothers with infants aged zero2 to six months at Ahero Sub District Hospital in Nyando District, Kenya. A cross- sectional design was conducted to 117 breastfeeding mothers at Ahero Sub-District Hospital at Maternal Child Health clinic; these were selected consecutively until the desired sample was attained. The independent variables were maternal education, marital status, both maternal and child age, maternal employment status, health factors (place of delivery and maternal chronic illness), and cultural beliefs while dependent variables included EBF practice and mothers’ knowledge of EBF3 (awareness of EBF and its benefits), pre lacteal feeds and exclusive breastfeeding consistency. Exclusiveness was measured in time initiated (30 minutes initiation after birth) Data were collected by trained enumerators who administered a structured questionnaire. Analysis was done using Statistical Package for Social Scientists (SPSS) by running frequencies and cross tabulation. Chi square test was used to check for strength of association between variables at 95% confidence level. The study found that there was low EBF practice (33%) in the area and this posed a great concern. It was established that marital status, employment, maternal education, place of delivery and both infant and mothers’ age were closely associated with knowledge and practice of EBF. Marital status and employment were strong predictors of both knowledge and practice which showed statistical significance of P= 0.02 and P=0.00, respectively. It was evident that family support is a key factor in the success of EBF with special focus on partner involvement. Actions to empower women and promotion of EBF campaign are recommended to achieve the fourth Millennium Development Goal (MDG) and probably reduce infant mortality in the area. Further studies are required to assess the impact of a strong focused educational program (focused on building family support) on improving EBF rates.