The racial origin is one of the main risk determinants of Staphylococcus aureus colonization and infection. For some time now, indigenous communities have been shown to be more prone to these risks as they present S. aureus strains different from those usually found in non-native populations. Culturally typical characteristics among different populations, such as overcrowded living conditions, lack of health assistance, and poor hygiene conditions can be more relevant to the pathogenesis of some S. aureus infections. Therefore, the indigenous people are definitively a risk group for the carriage of resistant microorganisms, and are susceptible to both acquisition and dissemination of infections. This study aimed to identify the prevalence and the risk factors for nasal and oral carriage of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) in indigenous communities from the North and Southeast regions of Brazil by evaluating the genetic diversity, dissemination, virulence factors, and antimicrobial resistance associated to ethnic, demographic, environmental, and behavioral issues. To this end, nasal and oropharyngeal samples of 443 indigenous people (116 from the Southeast and 284 from the North) were collected with sterile swabs. Then, such samples were seeded in culture medium and identified by conventional methods. Meanwhile, clinical and demographic data from the subjects were collected. S. aureus isolates were phenotypically and genetically tested for oxacillin/methicillin susceptibility and the staphylococcal cassette chromosome mec (SCCmec) was characterized. The virulence genes identification was carried out by Polymerase Chain Reaction (PCR). The characterization of the clonal profile was performed by The Pulsed Field Gel Electrophoresis (PFGE) to identify the endemic clusters in the population. In order to identify clusters of related genotypes, Multilocus Sequence Typing (MLST) was performed. The results showed a general prevalence rate of S. aureus of 47.6% (CI 95%: 42.64-52.64), while in the Southeast region there was a total of 43.1% (CI 95%: 33.94-52.62) and in the Amazon region 49.4% (CI 95%: 43.50-55-45). When the colonization sites were distributed, the rates were 31.8% (CI 95%: 27.23-36.82) of nasal carriage and 25.7 (CI 95%: 21.53-30.55) of oral carriage. Regarding the mecA gene detection, 3 isolates were positive, being 3 oral isolates. All the positive mecA samples harbored the SCCmec IV. Thus, the prevalence of MRSA in the study was 0.7% (CI 95%: 0.19-2.37). No resistant sample was identified in the Southeast region. With the detection of virulence genes, a higher percentage of genes related to hemolysins hla 96.3 and hld 80.6% and genes associated with the production of biofilm icaA 82.2 and icaD 72.7% could be evidenced. The identification of the clonal profile through the characterization by PFGE evidenced 21 clusters (>80% similarity) among the native populations of both states in which 5 major clones clustered samples both from the Southeast and from the Amazon. When the MSLT analysis was carried out, a prevalence of clonal complex ST 5 was identified, which clustered samples both from MSSA and MRSA, suggesting a probable common origin. The epidemiological results showed an association between the ethnicity factor and the prevalence of S. aureus. This study brings pioneering data about the epidemiology of Staphylococcus aureus and MRSA among Brazilian indigenous populations. The analysis of the clonal profile promotes the elucidation of questions related to the evolution process of the bacterium studied, suggesting a probable common origin among the different strains found. Finally, the epidemiological results allow us to infer that the factor ethnicity factor is related to the prevalence of S. aureus in human populations.