Poor oral health conditions in adults are associated with chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey. Tooth count was categorized into 4 groups, and chronic pain was defined as persistent pain lasting over 3 months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented greater odds of chronic pain (adjusted odds ratio [aOR] = 2.111, 95% confidence intervals (CI) = 1.213–3.676 for patients with 1–8 teeth). Edentulous participants presented with significantly higher odds of chronic pain in the lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR = 4.004, 95% CI = 2.766–5.798), variables of higher chronic pain included smoking (aOR = 1.518, 95% CI = 1.228–1.878), and hypertension (aOR = 1.463, 95% CI = 1.013–2.112). On the contrary, being Mexican American (aOR = .603, 95% CI = .414–.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis.