BACKGROUND: The Infant Mortality Rate assesses the deaths occurring in children under one year of age and serves as an important health indicator in mapping the living conditions of a given society. The aim of the present study is to evaluate the epidemiological trends of infant mortality in Brazil from 2000 to 2020, based on the most prevalent chapters of the International Classification of Diseases. METHODS: This is an ecological and retrospective study conducted using secondary data collection. The country of origin for the study is Brazil. The dependent variable of the study is infant mortality, specifically referring to children under one year of age. The independent variables include sex, color, and birth weight. The period analyzed spans from 2000 to 2020. The statistical processing was conducted using Joinpoint and GeoDa. RESULTS: In the analyzed period, the most prevalent causes of infant mortality, classified according to the ICD, were: conditions originating in the perinatal period, congenital malformations, infectious and parasitic diseases, respiratory diseases, and external causes of morbidity and mortality. It is noteworthy that the majority of the causes of death in children under one year of age exemplified in this study exhibited a declining trend, except for congenital malformations, deformities and chromosomal anomalies. In addition, external causes of mortality varied greatly throughout the historical series and, when analyzing more specifically the categories in this chapter, it was found that transport accidents are the main cause of death in children under one year of age. When observing the spatial distribution of infant mortality by RIAUs, it is noticeable that the Boa Vista region presented the highest infant mortality rate in the analyzed historical series, exceeding 3,795 deaths per 100,000 infants. CONCLUSIONS: Brazil has made progress over the years in public policies aimed at reducing infant mortality in the country, particularly through the consolidation and intensification of Primary Health Care coverage, which provides health promotion, protection, and recovery by identifying the main health risks and needs of each locality. However, addressing the health determinants that influence infant mortality requires actions that go beyond the health sector.