The purpose of this study was to determine the incidence of HPV-positive (HPV+) and HPV-negative (HPV-) head and neck cancer (HNC) in the American Indian/Alaska Native (AI/AN) population in California to assess whether incidence is higher among AI/ANs compared to other ethnicities. We analyzed data from the California Cancer Registry, which contains data reported to the Cancer Surveillance Section of the Department of Public Health. A total of 51,289 HNC patients were identified for the years 2009-2018. Outcomes of interest included sex, stage at presentation, 5-year survival rate, tobacco use, and HPV status. AI/AN and White patients had the highest burden of late stage HNC (AI/AN 6.3:100,000; 95% CI 5.3-7.4, White 5.8:100,000; 95% CI 5.7-5.9) compared to all ethnicities or races (Black: 5.2; 95% CI 4.9-5.5; Asian/Pacific Islander: 3.2; 95% CI 3-3.3; and Hispanic: 3.1; 95% CI 3-3.2 per 100,000). Additionally, AI/AN and White patients had the highest burden of HPV+ lip, oral cavity, and pharynx HNC (AI/AN 0.9:100,000; 95% CI 0.6-1.4, White 1.1:100,000; 95% CI 1-1.1) compared to all ethnicities or races (Black: 0.8:100,000; 95% CI 0.7-0.9; Asian/Pacific Islander: 0.4; 95% CI 0.4-0.5; and Hispanic: 0.6; 95% CI 0.5-0.6). AI/ANs had a decreased 5-year survival rate compared to White patients (AI/AN 59.9%; 95% CI 51.9-67.0% and White 67.7%; 95% CI 67.00-68.50%) and a higher incidence of HNC in former and current tobacco users. These findings underscore the disparities that exist in HNC for California AI/AN populations. Future studies should aim to elucidate why the unequal burden of HNC outcomes exists, how to address increased tobacco usage, and HPV vaccination patterns to create culturally and community-based interventions.