In this paper, we measure the effect of the 2020 COVID-19 pandemic wave at the national and subnational levels in selected Latin American countries that were most affected: Brazil, Chile, Ecuador, Guatemala, Mexico, and Peru. We used publicly available monthly mortality data to measure the impacts of the pandemic using excess mortality for each country and its regions. We compare the mortality, at national and regional levels, in 2020 to the mortality levels of recent trends and provide estimates of the impact of mortality on life expectancy at birth. Our findings indicate that from April 2020 on, mortality exceeded its usual monthly levels in multiple areas of each country. In Mexico and Peru, excess mortality was spreading through many areas by the end of the second half of 2020. To a lesser extent, we observed a similar pattern in Brazil, Chile, and Ecuador. We also found that as the pandemic progressed, excess mortality became more visible in areas with poorer socioeconomic and sanitary conditions. This excess mortality has reduced life expectancy across these countries by 2–10 years. Despite the lack of reliable information on COVID-19 mortality, excess mortality is a useful indicator for measuring the effects of the coronavirus pandemic, especially in the context of Latin American countries, where there is still a lack of good information on causes of death in their vital registration systems.