Background <p>Neonatal mortality remains a critical public health challenge in Ghana. Identifying key determinants is essential for designing targeted interventions to reduce newborn deaths.</p> Methods <p>This study analysed data from the 2022 Ghana Demographic and Health Survey (DHS) using binary logistic regression in SPSS version 30 to assess factors influencing neonatal mortality.</p> Results <p>Maternal education, socioeconomic status, and healthcare access significantly impacted newborn survival. Neonates born during the early neonatal period (1–8 days) faced higher mortality risks than those in the late neonatal phase (9–28 days). Adverse maternal pregnancy history, lack of tetanus toxoid vaccination during pregnancy, and low maternal education levels increased neonatal mortality risk. Conversely, neonates whose mothers had secondary or higher education exhibited lower mortality risks compared to those with uneducated mothers. Household wealth also played a role, with neonates from the third wealth quintile experiencing lower mortality rates compared to those from the poorest households. Neonatal mortality was associated with maternal, child, and household factors, with significant geographic disparities in mortality levels.</p> Conclusion <p>To reduce neonatal mortality, Ghana must enhance maternal healthcare access, promote antenatal and postnatal care attendance, and prioritise vaccinations and education for women. Targeted interventions addressing socioeconomic and regional disparities are crucial for improving newborn survival rates.</p>