Introduction: Promoting basic newborn care skills and practices is a cost-effective approach to improving newborn health outcomes. Therefore, this study aimed to assess the essence of the essential knowledge about newborn care, practices and related factors among nurse and midwives in western Ethiopia.Objective: This study intended to assess factors associated with Practice and knowledge of Essential newborn care among nurse and midwives working in Assosa Zone governmental health facility, western Ethiopia, 2021. Methods: Institutional based cross-sectional study design was conducted among nurses and Midwives those engaged in newborn care services in selected public health facilities in Assosa Zone western Ethiopia. A Convenient sampling technique was applied. Data was collected by interviewer administered structured questionnaires.Data processing and analysis: The collected data was entered into Epi data 3.1version and analyzed by using SPSS version 26. The strength of association between independent and dependent variables was measured by odd ratios with 95% CI at p-value of < 0.05. Result: 98% nurses and midwives w. Mean value of good knowledge and good practice of essential newborn care were 61.7% [95% CI (56.4, 69.8)] and 41.5% [95% CI (38.3, 48.5)] respectively. Being trained, educational qualification, availability of newborn care materials and work experience were significantly associated with knowledge practice of essential newborn care.Conclusion: This study identified that knowledge of essential newborn care was average among Nurse and Midwifes; however, the practice of essential newborn care was very low compared to other studies in Ethiopia. Therefore factors identified; in service training, improving educational qualification and increasing accessibility of new born care materials at all facility level are interventional areas to bring required knowledge and practice of Essential new born care.