This paper investigated the determinants of maternal mortality across sixteen West African nations from 2000 to 2022, employing robust econometrics methods such as Pooled Mean Group (PMG) and Fully Modified Ordinary Least Square (FMOLS). Grounded in life-course perspective theory, the study explored the interplay between clinical determinants and socio-economic factors including life expectancy, political stability, fertility rate, HIV prevalence, education, and healthcare expenditure. Findings unveil significant long-run and short-run determinants affecting maternal mortality. While life expectancy exhibits a statistically insignificant negative relationship in the PMG model, the FMOLS model highlights a significant negative association, emphasizing methodological robustness. Contrarily, political stability, initially appearing positively significant, loses significance in the FMOLS model, indicating nuanced dynamics. The positive and highly significant connection between fertility rate and maternal mortality aligns with economic theory, highlighting the strain on healthcare resources. HIV/AIDS prevalence emerges as a notable determinant, urging targeted interventions. Health expenditure's nuanced relationship underscores the importance of effective utilization, advocating strategic investments. Education expenditure, while showing contradictory results, emphasizes the need for targeted education policies. Policy recommendations advocate for a multifaceted approach, prioritizing strategic investments in healthcare infrastructure, targeted HIV/AIDS programs, comprehensive family planning services, and education policies. Leveraging political stability for effective policy implementation is paramount, ensuring tangible improvements in maternal health outcomes in West Africa.