Abstract Human papillomavirus (HPV)-associated cancer burden is rising in the United States. Trends in the incidence by county-level income and smoking prevalence remain undescribed. We used the Surveillance, Epidemiology, and End Results 21 database to ascertain HPV-associated cancers during 2000-2018. Trends were estimated by county-level income and smoking prevalence quartiles. Anal and vulvar cancer incidence among women and anal cancer incidence among men increased markedly in the lowest-income counties, whereas the increases were slower in the highest-income counties (eg, for vulvar cancer, incidence increased 1.9% per year, 95% confidence interval [CI] = 0.9% to 2.9%, in the lowest-income counties vs 0.8% per year, 95% CI = 0.6% to 1.1%, in the highest-income counties). In recent years, cervical cancer incidence plateaued (0.0% per year [95% CI = −0.5% to 0.5%]) in the highest-income counties; in the lowest-income counties, the annual percentage change was 1.6% per year (95% CI = −0.7% to 4.0%). Counties with high smoking prevalence had marked increases in incidence compared with their counterparts (eg, anal cancer among men increased 4.4% per year [95% CI = 2.7% to 6.0%] for those living in counties with the highest smoking prevalence vs 1.2% per year [95% CI = 0.7% to 1.7%] for those living in counties with the lowest smoking prevalence). Improved and targeted prevention is needed to combat the widening disparities.