COVID-19 is a global pandemic with uncertain death rates. We examined county-level population morality rates (per 100,000) and case fatality rates by US region and rural-urban classification, while controlling for demographic, socioeconomic, and hospital variables. We found that population mortality rates and case fatality rates were significantly different across region, rural-urban classification, and their interaction. All significant comparisons had p < 0.001. Northeast counties had the highest population mortality rates (27.4) but had similar case fatality rates (5.9%) compared to other regions except the Southeast, which had significantly lower rates (4.1%). Population mortality rates were highest in urban counties but conversely, case fatality rates were highest in rural counties. Death rates in the Northeast were driven by urban areas (e.g., small, East Coast states), while case fatality rates tended to be highest in the most rural counties for all regions, especially the Southwest. However, on further inspection, high case fatality rate percentages in the Southwest, as well as in overall US counties, were driven by a low case number. This makes it hard to distinguish genuinely higher mortality or an artifact of a small sample size. In summary, coronavirus deaths are not homogenous across the United States but instead vary by region and population and highlight the importance of fine-scale analysis.