Background <p>Birth asphyxia is a significant cause of most perinatal mortality and morbidity worldwide. In Ethiopia, maternal medical conditions, such as pregnancy-induced hypertension and diabetes, have significantly contributed to the increase in neonatal morbidity and adverse birth outcomes. The study aimed to identify the determinants of birth asphyxia among neonates delivered in Southwest Shoa Zone public hospitals, Ethiopia.</p> Methods <p>A retrospective unmatched case-control study design was used among neonates delivered at a selected hospital in Southwest Shoa Zone, Ethiopia, between 20 August 2022 and 19 November 2022. Cases and controls were enrolled in a ratio of 1:2. The cases were newborns with birth asphyxia, Apgar score (Appearance, Pulse, Grimaces, Activity, and Respiration) &lt; 7 within the first five minutes at birth. Newborns without birth asphyxia with Apgar score ≥ 7 within the first five minutes at birth were selected as controls. For each enrolled case of birth asphyxia, two unmatched control newborns who delivered without birth asphyxia were enrolled in selected hospitals during the study period. Data were collected using structured questionnaires and medical records. The collected data were cleaned, coded and entered into Epi Info version 7, then exported to Statistical Package for Social Sciences version 26 for analysis. Multivariate logistic regression analysis was used to identify the determinants of birth asphyxia, with the level of significance set at p-value &lt; 0.05.</p> Results <p>The study revealed that the mean age of the case mothers was 27 years (SD = ± 7.3) and that of control mothers was 27.1 years (SD = ± 5.4). Meconium-stained amniotic fluid [AOR = 1.9; 95% CI (1.02–3.6)], pregnancy-induced hypertension [AOR = 5.8; 95% CI (2.65–13.63), instrumental delivery [AOR = 5.71; 95% CI (1.56 − 28.2)], post term [AOR = 9.68 95% CI (1.87–26.87)], induction/augmentation of labor [AOR = 5.09; 95% CI (1.06–24.36)] and non-cephalic presentation [AOR = 1.68; 95%CI (0.24–7.55)] were significantly associated with birth asphyxia.</p> Conclusions <p>Birth asphyxia was significantly associated with maternal and obstetric factors, including meconium-stained amniotic fluid, pregnancy-induced hypertension, instrumental delivery, post-term, induction of labor and non-cephalic presentation. These findings highlight the importance of comprehensive maternal and newborn care, including strengthening antenatal care to identify and manage pregnancy-related complications, promoting maternal recognition of danger signs during pregnancy, and ensuring timely access to skilled intrapartum and emergency obstetric care to reduce the incidence of birth asphyxia.</p>