The basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0 of SARS-CoV-2 across U.S. counties. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0, and controlled for state-level effects using random intercepts. We also assessed whether the association was differential across county-level main mode of transportation percentage as a proxy for transportation accessibility, and adjusted for median household income. The median R0 among the United States counties was 1.66 (IQR: 1.35-2.11). A population density threshold of 22 people/km2 was needed to sustain an outbreak. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. An increase in one unit of log population density increased R0 by 0.16 (95% CI: 0.13 to 0.19). This association remained when adjusted for main mode of transportation and household income. The effect of population density on R0 was not modified by transportation mode. Our findings suggest that dense areas increase contact rates necessary for disease transmission. SARS-CoV-2 R0 estimates need to consider this geographic variability for proper planning and resource allocation, particularly as epidemics newly emerge and old outbreaks resurge.