BACKGROUND፡ Despite a global decline in under-five deaths, the neonatal mortality rate remains slow in developing countries and birth asphyxia remains the third cause of neonatal deaths. Globally, neonatal deaths accounts for 45% of under-five deaths, birth asphyxia causes 23-40% of neonatal deaths in Ethiopia.  There is limited data on risk factors of asphyxia in Ethiopia, particularly in the study area. Therefore, this study aimed to identify the risk factors of birth asphyxia among newborns.METHODS: This research followed a hospital-based unmatched case-control study design at Debre Markos comprehensive specialized referral hospital, Northwest Ethiopia, among 372 newborns (124 cases and 248 controls). Data were collected by interviewing index mothers and chart review using a pre-tested questionnaire. Then it was entered in Epi-data version 3.1 and transferred to STATA version 14.0 for analysis. Bivariate and multiple variable logistic regression were carried out to the possible risk factors. Finally, statistical significance was declared using adjusted odds ratio with 95% CI and p-value <0.05.RESULTS: Prolonged labor >12, meconium-stained amniotic fluid, assisted vaginal delivery, gestational age < 37 weeks, non-cephalic presentation, comorbidity, birthweight<2500grams were found to be significant factors of birth asphyxia.CONCLUSION: In this study, Prolonged labor >12 hours, meconium-stained amniotic fluid, assisted vaginal delivery, gestational age < 37 weeks, non-cephalic presentation comorbidity, fetal distress, birthweight<2500grams were found to be risk factors of birth asphyxia were risk factors of birth asphyxia. Therefore, to reduce neonatal mortality associated with birth asphyxia, attention should be given to holistic pregnancy, labor and delivery care, and post-natal care.  Moreover, interventions aimed at reducing birth asphyxia should target the identified factors.KEYWORDS: Birth asphyxia, Case-control study, risk factors, Ethiopia, Newborn