To document the evolution of the US life expectancy disadvantage and regional variation across the US states. I obtained life expectancy estimates in 2022 from the United Nations, the Human Mortality Database, and the US Mortality Database, and calculated changes in growth rates, US global position (rank), and state-level trends. Increases in US life expectancy slowed from 1950 to 1954 (0.21 years/annum) and 1955 to 1973 (0.10 years/annum), accelerated from 1974 to 1982 (0.34 years/annum), and progressively deteriorated from 1983 to 2009 (0.15 years/annum), 2010 to 2019 (0.06 years/annum), and 2020 to 2021 (-0.97 years/annum). Other countries experienced faster growth in each phase except 1974 to 1982. During 1933 to 2021, 56 countries on 6 continents surpassed US life expectancy. Growth in US life expectancy was slowest in Midwest and South Central states. The US life expectancy disadvantage began in the 1950s and has steadily worsened over the past 4 decades. Dozens of globally diverse countries have outperformed the United States. Causal factors appear to have been concentrated in the Midwest and South. Policies that differentiate the United States from other countries and circumstances associated with the Midwest and South may have contributed. ( 2023;113(9):970-980. https://doi.org/10.2105/AJPH.2023.307310).