PURPOSE: Limited data are available on the prevalence and clinical impact of Lynch syndrome (LS)-associated genomic variants in non-European ancestry populations. We identified and characterized individuals harboring LS-associated variants in the ancestrally diverse BioMe Biobank in New York City. PATIENTS AND METHODS: Exome sequence data from 30,223 adult BioMe participants were evaluated for pathogenic, likely pathogenic, and predicted loss-of-function variants in MLH1, MSH2, MSH6, and PMS2. Survey and electronic health record data from variant-positive individuals were reviewed for personal and family cancer histories. RESULTS: We identified 70 individuals (0.2%) harboring LS-associated variants in MLH1 (n = 12; 17%), MSH2 (n = 13; 19%), MSH6 (n = 16; 23%), and PMS2 (n = 29; 41%). The overall prevalence was 1 in 432, with higher prevalence among individuals of self-reported African ancestry (1 in 299) than among Hispanic/Latinx (1 in 654) or European (1 in 518) ancestries. Thirteen variant-positive individuals (19%) had a personal history, and 19 (27%) had a family history of an LS-related cancer. LS-related cancer rates were highest in individuals with MSH6 variants (31%) and lowest in those with PMS2 variants (7%). LS-associated variants were associated with increased risk of colorectal (odds ratio [OR], 5.0; P = .02) and endometrial (OR, 30.1; P = 8.5 × 10-9) cancers in BioMe. Only 2 variant-positive individuals (3%) had a documented diagnosis of LS. CONCLUSION: We found a higher prevalence of LS-associated variants among individuals of African ancestry in New York City. Although cancer risk is significantly increased among variant-positive individuals, the majority do not harbor a clinical diagnosis of LS, suggesting underrecognition of this disease.