Pre-exposure prophylaxis (PrEP) is a drug regimen recommended for anyone at high risk of getting HIV to prevent them from being infected. Little research exists on how state-level policies might be related to differential PrEP uptake across the United States. To better understand the associations between state-level policies and PrEP uptake, we examined HIV criminalization, nondiscrimination laws for sexual and gender minorities, Medicaid expansion, Ryan White funding, and sociodemographic characteristics in relation to the PrEP-to-need ratio, a measure of PrEP uptake. Using a cross-sectional design, we analyzed data from all fifty states; Washington, D.C.; and Puerto Rico (all of which we categorize as states here) regarding policy, socioeconomic factors, and PrEP-to-need ratio in 2018. States with HIV criminalization laws had lower PrEP-to-need ratio, and states with more nondiscrimination laws for sexual and gender minorities had higher PrEP-to-need ratio. We found no association between Medicaid expansion, Ryan White funding, percentage Hispanic, percentage uninsured, median household income, percentage with high school education, or state population and PrEP uptake. Legislators should consider how laws concerning HIV and sexual and gender minorities might protect against discrimination and subvert fear and stigma, given the potential impact of these policies on HIV prevention.