Research is limited on the effect of racism and social determinants of health on HIV pre-exposure prophylaxis (PrEP) use. This study used the PrEP-to-Need Ratio (PNR), which measures PrEP prescriptions divided by HIV diagnoses in the county, to evaluate sufficient PrEP use. AIDSVu datasets were compared to county-level social determinants of health. Standardized regression coefficients (β) were compared to identify strongest associations with PNR. Overall, factors including percent African American and percent uninsured had negative correlations with PNR, whereas median household income and severe housing cost burden had positive associations. Stratifying for population size, percent African American, percent uninsured, and severe housing cost burden were significant for low population areas, whereas median household income, percent in poverty, percent uninsured, and percent African American were significant for large populations. To reduce PrEP disparities, public health must develop strategies to reach those most in need, especially historically disadvantaged communities.