Background The first one month of life; the neonatal period is the most risky time for child survival. In Ethiopia, neonatal mortality is unacceptably high, and the trend in reduction is slower as compared to infant and child mortality. The magnitude and associated factors of neonatal mortality in a tertiary care facility were not well documented. Therefore, the aim of this study was to determine neonatal mortality and predictors among neonates admitted to neonatal intensive care unit of Wolaita Sodo University Teaching and Referral Hospital, South Ethiopia. Methods A retrospective cohort study design was done among neonates admitted to neonatal intensive care unit of a University Teaching and Referral Hospital from 2015 to 2017. Data were collected using data extraction checklist from the medical registry. The main outcome was the occurrence of death within the first four weeks. The survival time was calculated in days between the date of admission and the date of death. Kaplan-Meier survival was used to depict the pattern of death in 28 days and Cox-Proportional model was used to identify the predictors of the neonatal mortality. Results A total of 964 neonates which contributed to 5889 neonates-days were included in the study. There were 159 neonatal deaths during the follow-up time. Overall, the neonatal mortality incidence was 27 per 1000 neonates-days. Predictors of neonatal mortality were: multiple birth, mothers who did not attend antenatal care visits, neonates born by cesarean section, not initiated breast feeding within 1 h of birth, neonates resuscitated, hyaline membrane disease and perinatal asphyxia. Conclusion Neonatal mortality at neonatal intensive care unit was high. Managing neonatal complications, initiating breast feeding within 1 h of birth, promoting antenatal care visits, improving quality of services and ensuring continuum of care are recommended to increase survival of neonates.