Bioarchaeologists have long noted two unusual trends in the dentitions of prehistoric Native Californian populations: high rates of wear and low prevalence of caries. The Central California site of CA-CCO-548 offers a unique opportunity to examine the relationship between oral pathology and extreme dental wear in a large (n = 480), ancient (4,300–3,100 BP), and temporally well-defined population sample. This study specifically examines three interrelated processes of the oral cavity in this population: dental wear, dental caries, and periodontal disease. The results show high levels of dental wear (average of 6.1, Smith system), low frequencies of carious lesions (2.5%), low frequencies of periodontal disease (17.8%), and high frequencies of periapical abscesses (10.7%). The pathological processes examined here have complicated multifactorial etiologies. However, they all share the common primary etiological agents of facultative pathogenic bacteria proliferation in the oral biofilm. Integration of the current etiological explanations for infections of the oral cavity, information from the ethnographic record pertaining to subsistence and activity patterns in Native Californian populations, and statistical analysis of specific disease and wear patterns leads to a novel explanation for the observed pattern of oral pathology in this population sample. Specifically, the introduction of antibacterial compounds through dietary items and non-alimentary tooth use is suggested as the most likely explanation for the unusually low prevalence of dental caries and periodontal disease. Am J Phys Anthropol 154:171–188, 2014. © 2014 Wiley Periodicals, Inc.