Background: - Perinatal asphyxia is the third leading cause of neonatal mortality globally, which usually happens within the first week of life. Therefore, evidence-based estimation of neonatal mortality is a cornerstone for tracking progress towards child survival goal and identifying priority areas to improve progress towards eliminating preventable deaths due to perinatal asphyxia. Objective: To assess incidence and predictors of mortality among neonates with perinatal asphyxia admitted to the neonatal intensive care unit of Debre Markos Comprehensive Specialized Hospital, 2021.Methods: An institutional-based retrospective follow-up study was conducted among 402 neonates with perinatal asphyxia (PNA) admitted to the neonatal intensive care unit (NICU) of Debre Markos Comprehensive Specialized Hospital from January 1st, 2018 to the 30th of December, 2020. A simple random sampling technique was used to select the estimated sample. Data were entered using Epi data Version 4.6.0.0 and analyzed using Stata Version 14. The Kaplan–Meier and log-rank test were used to estimate and compare the survival time. Both the bi-variable and multivariable Weibull regression models were fitted to identify predictors of mortality. Finally, the Hazard ratio with a 95%CI was computed, and variables with p-values <0.05 were considered as statistically significant predictors of mortality. Results: A total of 125 (31.09%) neonates died during the follow-up period. The overall incidence rate of mortality was found to be 53.49 per 1000 neonate-days of observations (95%CI: 44.89-63.74). Neonatal sepsis (AHR=2.13;95%CI: 1.38-3.27), preterm birth (AHR= 3.42 95%CI; 2.13- 5.48), Hypoxic Ischemic Encephalopathy stage II (AHR=6.65 95%CI: 2.57-17.26), and III (AHR=16.8 95%CI; 6.28- 44.9), Antepartum hemorrhage (AHR=2;95%CI: 1.13-3.92), the induced onset of labor (AHR=3.90;95%CI; 1.83-8.27), and post-partum hemorrhage (AHR=2.12;95%CI: 1.32-3.38) were significant predictors of mortality among neonates with perinatal asphyxia.Conclusion: The study found that the overall incidence rate of mortality among neonates with PNA remains high. Neonatal sepsis, Hypoxic-ischemic encephalopathy stage II and III, preterm birth, antepartum hemorrhage, postpartum hemorrhage and induced onset of labor were independent predictors of mortality. Therefore, early anticipating high-risk pregnancies and newborns with the respective intervention could reduce neonatal due to perinatal asphyxia.