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Background Oropharyngeal cancer (OPC) is a major head and neck cancer subtype with shifting U.S. epidemiology. We performed a surveillance-style analysis of OPC mortality trends and demographic/geographic disparities, 1999–2023. Methods OPC mortality (1999–2023) was obtained from CDC WONDER. Age-adjusted mortality rates (AAMRs) were computed by category. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC). Pearson correlation assessed associations between AAMR and structural indicators. Results From 1999 to 2023, 51,719 OPC-related deaths were recorded. AAMR increased from 0.75 (1999) to 1.17 (2023), with a relatively stable pattern during 1999–2009 (APC = 0.42; 95% CI: −0.47 to 1.32) followed by an increase during 2009–2023 (APC = 3.02; 95% CI: 2.59 to 3.46); the AAPC for 1999–2023 was 1.93 (95% CI: 1.51 to 2.36; p < 0.001). Mortality was higher in males (AAMR = 1.44; 95% CI: 1.37 to 1.52) than in females (0.37; 95% CI: 0.34 to 0.41), with increases in both groups (AAPC: 2.16; p < 0.001 vs 1.13; p = 0.001 ). By race/ethnicity, overall AAMR was higher among non-Hispanic Black individuals (1.18; 95% CI: 1.03 to 1.32) but declined over time (AAPC = −1.12; p < 0.001; 95% CI: −1.76 to −0.47), whereas non-Hispanic White individuals increased (AAPC = 2.92; p < 0.001; 95% CI: 2.46 to 3.39) and exceeded non-Hispanic Black individuals in later years. AAMR increased across all U.S. census regions, with higher levels and/or faster increases in the Midwest and South. Nonmetropolitan areas increased faster than metropolitan areas (AAPC: 2.98; p < 0.001 vs 1.26; p < 0.001). State-level variation was observed; AAMR was inversely correlated with dentist density (r = −0.48, p = 0.010 ) and HPV vaccination coverage (r = −0.44, p = 0.018 ), while the correlation with poverty rate was positive but not statistically significant (r = 0.28, p = 0.152 ). Conclusion OPC mortality increased in the United States from 1999 to 2023, with demographic and geographic disparities. These surveillance findings may support public health monitoring and provide a hypothesis-generating basis for future analytic studies.