Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (T_H17) cells in human periodontitis. Phenocopying humans, T_H17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral T_H17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)–dependent manner, periodontitis-associated expansion of T_H17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23. T_H17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of T_H17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in T_H17 cell differentiation established human relevance for our murine experimental studies. In the oral cavity, human T_H17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of T_H17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis.