Objectives: This study used multilevel social determinants of health (SDoH) models to determine how SDoH influence different sexes of patients diagnosed with HPV-positive oropharyngeal squamous cell cancers (OPSCC) across the US. Methods: This was a retrospective cohort study assessing HPV-confirmed patients with oropharyngeal squamous cell cancers from 2010 to 2018 using census-level Yost Index socioeconomic status (SES) score and rurality–urbanicity measures alongside individual-level race–ethnicity while stratifying by biological sex. Age-adjusted multivariate regressions were performed for survival, treatment receipt, and delay of treatment initiation (of 3+ months). Results: Across 14,076 OPSCC-HPV-positive patients, delay of treatment uniquely featured positive predictors for males of black race–ethnicity (OR, 2.07; 95% CI, 1.68–2.54) and poor Yost SES (1.43; 1.24–1.65). Five-year all-cause mortality uniquely showed positive predictors of females of black race–ethnicity (2.74; 1.84–4.71) and of males with poor Yost SES (1.98; 1.79–2.19). Three-year all-cause mortality shared positive predictors across sexes but were exacerbated in females of black race–ethnicity (2.50; 1.82–3.44) compared to males (2.23; 1.91–2.60); this was reversed for poor Yost SES (male, 1.92, 1.76–2.10; female, 1.60, 1.32–1.95). Surgery showed negative predictors of black race–ethnicity that displayed worsened effects in females (0.60, 0.44–0.79) versus males (0.75, 0.66–0.86). First-line radiation receipt uniquely featured negative predictors for males of black race–ethnicity (0.73; 0.62–0.86) with poor Yost SES (0.74; 0.68–0.82). Conclusions: Comprehensive models of multilevel SDoH displayed exacerbated disparity effects of community-level SES in males and black race–ethnicity among female HPV-positive OPSCC patients. These objective comparisons of specific SDoH factors inform providers and policy direction on how to strategically target the most pertinent SDoH factors affecting a rapidly growing cancer population.