The COVID-19 pandemic has had intense, heterogeneous impacts on different communities and geographies in the United States. We explore county-level associations between COVID-19 attributed deaths and social, demographic, vulnerability, and political variables to develop a better understanding of the evolving roles these variables have played in relation to mortality. We focus on the role of political variables, as captured by support for either the Republican or Democratic presidential candidates in the 2020 elections and the stringency of state-wide governor mandates, during three non-overlapping time periods between February 2020 and February 2021. We find that during the first three months of the pandemic, Democratic-leaning and internationally-connected urban counties were affected. During subsequent months (between May and September 2020), Republican counties with high percentages of Hispanic and Black populations were most hardly hit. In the third time period –between October 2020 and February 2021– we find that Republican-leaning counties with loose mask mandates experienced up to 3 times higher death rates than Democratic-leaning counties, even after controlling for multiple social vulnerability factors. Some of these deaths could perhaps have been avoided given that the effectiveness of non-pharmaceutical interventions in preventing uncontrolled disease transmission, such as social distancing and wearing masks indoors, had been well-established at this point in time.