Background: Homicide was the fifth cause of death in Mexico in 2019 and has been among the top ten causes of death since 2009. Despite its relevance, homicide has neither been considered a public health problem by health authorities nor has been a point of focus for the development of effective prevention strategies, compared to other leading and preventable causes of death. This study aims to establish homicide as a relevant public health problem in Mexico. Methods: We analyzed publicly available data in Mexico from 1998 to 2019 to calculate homicide rates and compare them to other causes of death stratified by age and sex. We also described the age, period, and cohort trends of homicides. Findings: Homicide has been the leading cause of death for both sexes for several age groups since 2010, surpassing cardiovascular disease, diabetes mellitus, cancer, and accidents. Since 2018, homicides have been the main cause of death for females 15 to 24 years old and the second cause of death for 25 to 34 years old. Males 25 to 34 years old experienced the highest homicide rates across all the study period, exceeding 1 per 1,000 in 2019. Interpretation: Homicides are one of the major causes of death in Mexico and currently represent a national public health threat. This study reveals important patterns of homicide deaths that can inform national and regional public health policy. Funding: This study was supported by grants from Open Society Foundations (OSF) and the Drug Policy Program at CIDE. Declaration of Interests: FAE reports funds from Open Society Foundations (OSF) and the Drug Policy Program at CIDE. All authors declare no competing interests.