Background. Knowledge of essential newborn care and proper practice is important for the survival, growth, and development of a newborn. In spite of its essentiality, most health-care professionals do not know and follow the World Health Organization recommendation. Therefore, this study is aimed at assessing knowledge of essential newborn care and associated factors among nurses and midwives working in maternal health case team at public health facilities of Wolaita Zone, Ethiopia, 2019. Methods. Institution-based cross-sectional study design was conducted from March to April 2019. Data were collected by using pretested questionnaire, and 36 public health facilities were selected after stratifying them based on their level of service and number of nurses and midwives working in maternal health-care team. All 218 nurses and midwives who were working in the delivery unit from selected facilities were included in the study. The collected data were entered into Epi data 3.02 and exported to statistical software for social sciences version 22 for analysis. Descriptive, bivariate, and multivariate analyses were done. Statistical significance of variables was declared as a p value<0.05, and strength of association was adjusted odds ratio at 95% confidence interval in the final model. Result. A total of 218 nurses and midwives were participated in the study. Among them, 57.9% of participants had good knowledge of essential newborn care. The type of profession (AOR=5.79, [2.47, 13.58]), educational level (AOR=3.26, [1.42, 7.52]), interest to work in delivery room (AOR=4.85, [1.89, 12.42]), and presence of guidelines (AOR=2.29, [1.18, 4.45]) were the factors significantly associated with having knowledge of essential newborn care. Conclusion and Recommendation. The nurses and midwives had poor knowledge of some components of essential newborn care in the study area. Bachelor level of study, interest to work in delivery room, and being a midwife were the factors independently associated with knowledge of essential newborn care among nurses and midwives. Therefore, the head of labor ward and institution, zonal and woreda health units, and nongovernmental organizations who are working on maternal and child health should work on providing continuous education, providing incentives and motivators to improve interest to work in delivery unit, and providing guidelines in the unit.