Purpose To investigate the global prevalence of the JP2 genotype of Aggregatibacter actinomycetemcomitans (Aa). Methods A comprehensive electronic search of databases, PUBMED, MEDLINE, EMBASE, BIOSIS, and SCOPUS, was conducted up to August 2021. All published articles and studies were considered, excluding animal studies, editorials, personal opinions, letters to editor, conference abstracts, posters, and those studies without full text. The primary objective of this systematic review was to determine the presence of the JP2 genotype of Aa in the world population. Results A total of 295 articles were identified, of which 62 were preselected, and 51 were finally included in this review. Due to variable study designs and high heterogeneity, a meta-analysis was not conducted. A total of 9744 subjects were screened for the presence of the JP2 genotype of Aa worldwide, and only 621 cases were found positive. Conclusions A relatively high presence of JP2 genotype of Aa was found in subjects from South America, North America, and Africa. There were no studies estimating the presence of the JP2 genotype of Aa in the Oceania region. The heterogeneity and quality of the included publications suggest that caution should be exercised when interpreting the data and that there remains an important need for additional evidence. Clinical relevance. Periodontitis is a highly prevalent infammatory oral disorder with substantial aesthetic, functional, and psychological implications for patients. The JP2 genotype of Aa is implicated in the pathogenesis of periodontitis. To the best of our knowledge, there is a lack of systematic reviews estimating the presence of the JP2 genotype of Aa in the global population. We identified a relatively high presence of the JP2 genotype of Aa in specific geographic areas of the world, and we propose that cross-sectional and longitudinal studies are lacking in the Oceania region and need to be conducted to estimate the presence of the JP2 genotype of Aa in this region.