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Background and Aim: Neonatal sepsis is a systemic inflammatory response to infection during the first 4 weeks of an infant's life. It is a significant cause of neonatal morbidity and mortality in low‐ and middle‐income countries. This study aimed to determine the predictors of the onset of sepsis at the Neonatal Intensive Care Unit of the Tamale Teaching Hospital, Ghana. Methods: A cross‐sectional study was conducted among 275 mothers and their singleton neonates diagnosed clinically with sepsis. A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early‐onset (EOS) and late‐onset sepsis (LOS), respectively. Results: Single motherhood (AOR = 1.882, 95% CI = 0.926−3.822, p =.08) and home delivery (AOR = 3.667, 95% CI = 0.584−23.026, p =.17) were predictors of EOS, with single motherhood being the predictor for LOS (AOR = 2.906, 95% CI = 0.715−11.805, p =.14) in a univariate analysis. When maternal occupation was adjusted for in a multivariate analysis, single mother (AOR = 2.167, 95% CI = 1.010−4.648, p =.04) was the main predictor of EOS, with low neonatal birth weight being the main predictor of LOS (AOR = 0.193, 95% CI = 0.038−0.971, p =.04). Conclusion: Maternal marital status is a significant predictor of both EOS and LOS, with predictors of EOS being lower gestational age and low birth weight, while for LOS, low birth weight is the main predictor. Findings from this study can serve as a commencement point for developing predictive models for the onset of sepsis in neonates in the study facility. Key points: What is known: Neonatal sepsis is a medical emergency. What is new: Predictors for the identification of early and late‐onset sepsis in a resource‐poor setting have been identified in this study. The clinical implications of this study: Findings from this provide a valuable reference for the early identification of neonatal sepsis to improve clinical outcomes. Also, the findings in this study will serve as a commencement point for developing predictive models for identifying the onset of sepsis in neonates in resource‐poor settings in Sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]