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Background: The work of the WHO Commission on the Social Determinants of Health has been fundamental to provide a conceptual framework of the social determinants of health. Based on this framework, this study assesses the relationship of income inequality as a determinant of neonatal mortality in the Americas and relates it to the achievement of the Sustainable Development Goal target 3.2 (reduce neonatal mortality to at least as low as 12 deaths per 1,000 live births). The rationale is to evaluate if income inequality may be considered a social factor that influences neonatal mortality in the Americas. Methods: Yearly data from 35 countries in the Americas during 2000–2019 was collected. Data sources include the United Nations Inter-agency Group for Child Mortality Estimation for the neonatal mortality rate (measured as neonatal deaths per 1,000 live births) and the United Nations University World Institute for Development Economics Research for the Gini index (measured in a scale from 0 to 100). This is an ecological study that employs a linear regression model that relates the neonatal mortality rate (dependent variable) to the Gini index (independent variable), while controlling for other factors that influence neonatal mortality. Coefficient estimates and their robust standard errors were obtained using panel data techniques. Results: A positive relationship between income inequality and neonatal mortality is found in countries in the Americas during the period studied. In particular, the analysis suggests that a unit increase in a country's Gini index during 2000–2019 is associated with a 0.27 (95% CI [− 0.04, 0.57], P =.09) increase in the neonatal mortality rate. Conclusion: The analysis suggests that income inequality may be positively associated with the neonatal mortality rate in the Americas. Nonetheless, given the modest magnitude of the estimates and Gini values and trends during 2000–2019, the findings suggest a potential limited scope for redistributive policies to support reductions in neonatal mortality in the region. Thus, policies and interventions that address higher coverage and quality of services provided by national health systems and reductions in socio-economic inequalities in health are of utmost importance. [ABSTRACT FROM AUTHOR]