The COVID-19 pandemic was accompanied by an unprecedented influx of misinformation often with adverse impact on the effectiveness of institutional responses to the health crisis. However, relatively little is still known about the factors that may have facilitated the proliferation and public acceptance of misinformation related to the virus or to the government’s anti-pandemic measures, particularly in comparative perspective. Utilizing data collected by a representative cross-country survey ( N = 5,000) in four countries led by populist leaders during the pandemic—Brazil, Poland, Serbia, and the United States—this study explores the links between three mutually interrelated factors, namely media usage across different platforms, affinity to populism, and trust in scientific expertise, and people’s beliefs in selected COVID-related misinformation. The findings show that preexisting attitudes, especially affinity to populism and mistrust in experts, are generally stronger predictors of people’s likelihood to endorse misinformation related to the pandemic than their news consumption patterns. Nevertheless, the analysis also indicates an important role played by exposure to specific media brands, particularly those promoting a skeptical stance toward preventive measures and COVID-19 vaccines, as well as messaging apps, which display stronger relationship with misinformation beliefs than social networking sites. The article concludes by discussing implications for practical efforts to combat misinformation, especially during a health crisis.