Efforts to reverse the physical inactivity (PI) and obesity pandemics in the United States (U.S.) have been unsuccessful. This commentary provides a view of PI and obesity in the U.S. from the intersection of politics, socioeconomics, race, and culture. On a national level, counties where the Democratic presidential candidate received more votes in 2020 than the Republican candidate had a lower PI and obesity prevalence. The percentage completing some college and Black individuals as well as median household income were higher in counties where the Democratic candidate received more votes. Regionally, unique, region-specific cultural identities and partisan coalition demographics were apparent and serve as potential explanations for inconsistencies in PI and obesity prevalence across the U.S. Identifying the driving forces of PI and obesity within specific U.S. regions and crafting messaging that has optimal efficacy on a local level is essential to reducing the burden of cardiovascular disease and other chronic conditions.