species are abundant members of the human oral microbiome with multiple interspecies commensal relationships. Examining the distribution patterns of species across the oral cavity is fundamental to understanding their oral ecology. In this study, we used a combination of pangenomic analysis and oral metagenomic information to clarify taxonomy and to test the site specialist hypothesis for the genus, which contends that most oral bacterial species are adapted to live at specific oral sites. Using isolate genome sequences combined with shotgun metagenomic sequence data, we showed that species have clear, differential site specificity: Veillonella parvula showed strong preference for supra- and subgingival plaque, while closely related V. dispar, as well as more distantly related V. atypica, preferred the tongue dorsum, tonsils, throat, and hard palate. In addition, the provisionally named sp. Human Microbial Taxon 780 showed strong site specificity for keratinized gingiva. Using comparative genomic analysis, we identified genes associated with thiamine biosynthesis and the reductive pentose phosphate cycle that may enable species to occupy their respective habitats. Understanding the microbial ecology of the mouth is fundamental for understanding human physiology. In this study, metapangenomics demonstrated that different species have clear ecological preferences in the oral cavity of healthy humans, validating the site specialist hypothesis. Furthermore, the gene pool of different species was found to be reflective of their ecology, illuminating the potential role of vitamins and carbohydrates in determining distribution patterns and interspecies interactions.