Background: Growing literature suggests that racial disparities exist in patients with head and neck squamous cell carcinoma (HNSCC). Currently, there are many hospital-based cohorts assessing racial disparities, however only a limited number of population-based cohorts exist. This study aims to explore the association between clinical characteristics and patient demographics with overall survival by race and HPV status. Methods: Patients were identified from the Carolina Head and Neck Cancer Study (CHANCE), a population based case-control study with enrollment from 2001-2006 in North Carolina. Vital status was determined by linkage with the National Death Index. Survival was considered at 5 years after diagnosis or study enrollment. We used Kaplan-Meyer analyses and Cox proportional hazards regression modeling to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 1361 HNSCC patients with no baseline metastasis and adequate survival time were identified. Of these, 1010 patients were white while 351 patients were black. Black patients were statistically more likely to be younger at age of diagnosis, have a history of tobacco or alcohol use, be uninsured, and not have completed high school (p-value < 0.001). In an unadjusted cox regression analysis, blacks had 1.50 times (95% CI 1.01-1.57) decreased overall survival than whites. Adjusting for gender, stage of disease, age, treatment, and smoking status, this relationship remained (HR 1.30, CI 1.1-1.6). In a subset analysis of male patients by disease site, there was decreased overall survival in black patients in oral cavity cases (p < 0.01). This relationship trended towards significant in pharynx cancer (p = 0.054) and was not found in laryngeal cancer. In pharyngeal cases only, there was decreased overall survival in black patients with HPV+ disease (p = 0.03) but not in HPV- cases (p = 0.33). Conclusions: This is the first population-based study that confirms racial disparities in HPV+ HNSCC. We also found worse overall survival prognosis for black patients with oral cavity cancer and a similar trend in pharynx cancer. Further studies are needed to evaluate if this difference is driven by either biological or socioeconomic factors.