Many people practiced COVID-19-related safety measures in the first year of the pandemic, but Republicans were less likely to engage in behaviors such as wearing masks or face coverings than Democrats, suggesting radical disparities in health practices split along political fault lines. We developed an “intervention tournament” which aimed to identify the framings that would promote mask wearing among a representative sample of Republicans and Democrats in the U.S. from Oct 14, 2020, to Jan 14, 2021 (N = 4931). Seven different conditions reflecting different moral values and factors specific to COVID-19 — including protection from harm (self), protection from harm (community), patriotic duty, purity, reviving the economy, threat, and scientific evidence — were implemented to identify which framings would “win” in terms of promoting mask wearing compared to a baseline condition. We found that Republicans had significantly more negative attitudes toward masks, lower intentions to wear them, and were less likely to sign or share pledges on social media than Democrats, which was partially mediated by Republicans, compared to Democrats, perceiving that the threat of COVID-19 was lower. None of our framing conditions significantly affected Republicans’ or Democrats’ attitudes, intentions, or behaviors compared to the baseline condition, illustrating the difficulty in overcoming the strength of political polarization during COVID-19.