Antimicrobial resistance is recognized as one of the most important global human health problems in the 21st century. The balance between clinical need and resistance prevention is further compromised by agricultural antibiotic use as some countries have actively used colistin in animal production. Antimicrobial-resistant microorganisms have been found in humans, food, animals, plants, and the environment (water, soil, and air), and they can move between ecosystems. The problem of antimicrobial resistance is currently seen in the concept: One Health. This approach encourages interdisciplinary collaborative efforts that work locally. The beginnings of the mcr gene's presence in America dates to 2012 and the first report of disseminating the mcr-1 gene was described for Kelp gulls (Larus dominicanus) from Ushuaia, Argentina. It can be associated with the possible dissemination of the gene in the American continent through migratory birds. The mcr-1 gene is disseminated in countries, such as Argentina, Brazil, Bolivia, Colombia, Chile, Ecuador, Paraguay, Peru, Uruguay, and Venezuela and the mcr-3 and mcr-9.1 gene in Brazil and mcr-5 in Colombia and Paraguay. Given this context, we present a literature review on disseminating the mcr gene and its variants in South America in a One Health approach.