BackgroundWest African countries experienced the highest under-5 mortality rate (U5MR), the lowest life expectancy, and the poorest economic development. This study aimed to explore the spatiotemporal trend of U5MR and spatial spillover effects of health resources and services to provide a basis for establishing health policies and international cooperative mechanisms in West Africa.MethodsWe retrieved data from the World Health Organization’s Global Health Observatory, the United Nations Human Development Report, and the Global Burden of Disease Study 2019. Joinpoint regression analysis and Moran’s I method were used to examine the temporal trend and spatial dependence of U5MR, respectively. Spatial regression analysis was used to examine the spatial spillover effects.ResultsThe long-term downward trends in U5MR were divided into multiple segments by two or three change points in 2013, 2014, or 2015, and the annual percentage change after 2015 was higher than before 2015. Global Moran’s I was positive, significantly indicating positive spatial autocorrelation, which increased from 0.2850 (p = 0.0210) to 0.3597 (p = 0.0080). Based on spatial regression analysis, human development index (HDI), physicians density, nurses and midwives density, health center density, percentage of infants lacking immunization for diphtheria and measles, and coverage rate of at least one antenatal visit had negative spatial spillover effects on U5MR. HDI had the strongest negative correlation (β = −0.0187 to −0.1054, p < 0.0001). Current health expenditure (CHE) per capita had positive spatial spillover effects on U5MR.ConclusionThis study revealed the spatiotemporal trend of U5MR in West African countries and spatial spillover effects of health resources and services. Promoting economic development, increasing health human resources, health expenditure, vaccination rate, antenatal care coverage, and the proportion of health professionals attending births not only reduced the local U5MR but also exerted spatial spillover effects on adjacent countries. The West African Health Organization may consider regional spillover mechanisms to develop regional health policy and intervention cooperation mechanisms, which will contribute to achieving the sustainable development goal on U5MR, Africa Agenda 2063, and universal health coverage.