question: BACKGROUND: Identifying county-level characteristics associated with high coronavirus 2019 (COVID-19) burden can help allow for data-driven, equitable allocation of public health intervention resources and reduce burdens on health care systems. METHODS: Synthesizing data from various government and nonprofit institutions for all 3142 United States (US) counties, we studied county-level characteristics that were associated with cumulative and weekly case and death rates through 12/21/2020. We used generalized linear mixed models to model cumulative and weekly (40 repeated measures per county) cases and deaths. Cumulative and weekly models included state fixed effects and county-specific random effects. Weekly models additionally allowed covariate effects to vary by season and included US Census region-specific B-splines to adjust for temporal trends. RESULTS: Rural counties, counties with more minorities and white/non-white segregation, and counties with more people with no high school diploma and with medical comorbidities were associated with higher cumulative COVID-19 case and death rates. In the spring, urban counties and counties with more minorities and white/non-white segregation were associated with increased weekly case and death rates. In the fall, rural counties were associated with larger weekly case and death rates. In the spring, summer, and fall, counties with more residents with socioeconomic disadvantage and medical comorbidities were associated greater weekly case and death rates. CONCLUSIONS: These county-level associations are based off complete data from the entire country, come from a single modeling framework that longitudinally analyzes the US COVID-19 pandemic at the county-level, and are applicable to guiding government resource allocation policies to different US counties. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-11060-9.