Ethnic inequalities are often associated with social determinants of health. This study seeks to identify the latest scientific evidence on inequalities in the health of people of African descent in the Americas. For this, a systematic review of the literature on health and people of African descent in the Americas was carried out in the LILACS, PubMed, MEDLINE, and IBECS databases. Institutional and academic repositories were also consulted. Evidence was obtained on the presence and persistence of health inequalities in the population of African descent in the Americas from the identification of five types of quantitative and qualitative evidence: (1) ethnic/racial concept and variables; (2) relations with other social determinants; (3) health risks; (4) barriers and inequalities in health services; and, (5) morbi-mortality from chronic diseases. Studies with qualitative methods revealed invisibility, stereotypes, and rejection or exclusion as main factors of inequality. This review evidenced the existence of health inequalities, its interconnection with other adverse social determinants and risk factors, and its generation and perpetuation by discrimination, marginalization, and social disadvantage. These conditions make people of African descent a priority population group for action on equity, as demanded by the 2030 Agenda for Sustainable Development.