Summary Background The Human Development Index (HDI)—a composite metric encompassing a population’s life expectancy, education, and income—is used widely for assessing and comparing human development and well-being at the country level; it does not, however, account for within-country inequality. In this study of the United States, we adapted the HDI framework to measure HDI at an individual level, allowing us to examine disparities in the distribution of well-being by race, sex, age, and geographical location. Methods We used individual-level data from the 2008–2021 American Community Survey (ACS) public use microdata sample. We subset to adults age 25 and older and extracted information on race, sex, age, location (Public Use Microdata Areas [PUMAs]), educational attainment, and household income and size. We merged these data with estimated life tables by race, sex, age, location (county), and year, generated using Bayesian small area estimation models applied to death certificate data from the National Vital Statistics System. For each individual in the ACS, we used these combined data to estimate years of education, household consumption, and expected lifespan; converted each of these three features into an index using a percentile score; and calculated HDI as the geometric mean of these three indices. Finally, we grouped individuals into yearly HDI deciles. Findings Years of education, household consumption, and expected lifespan—and thus HDI—varied considerably among adults in the USA. There were systematic differences in the distribution of HDI by race and sex from 2008 to 2021. In the lowest HDI decile—ie, the 10% of the population with the lowest HDI—American Indian or Alaska Native (AIAN) males (50% [SE 0.2], 0.37 [SE 0.002] million mean annual population in lowest HDI decile), Black males (40% [<0.1], 4.67 [0.006] million), AIAN females (23% [0.1], 0.19 [0.001] million), Latino males (21% [<0.1], 3.27 [0.006] million), Black females (14% [<0.1], 1.86 [0.004] million), and Latino females (13% [<0.1], 2.07 [0.006] million) were over-represented. Given differences in population size, however, White males were the largest population group in the lowest decile (27% [<0.1] of the lowest decile, 5.87 [0.012] million), followed by Black males (22% [<0.1], 4.67 [0.006] million), Latino males (15% [<0.1], 3.27 [0.006] million), White females (11% [<0.1], 2.46 [0.008] million), Latino females (10% [<0.1], 2.07 [0.006] million), and Black females (9% [<0.1], 1.86 [0.004] million). There were notable differences in these patterns by age group: for example, AIAN and Black males were even more over-represented in the lowest decile for ages 25–44 (66% [0.2], 0.22 [0.001] million AIAN males; 46% [<0.1], 2.52 [0.005] million Black males) compared to ages 85 and older (22% [1.1], <0.01 [<0.001] million AIAN males; 20% [0.3], 0.03 [<0.001] million Black males), whereas Asian males and females were under-represented among ages 25–44 (2% [<0.1], 0.07 [<0.001] million Asian males; 2% [<0.1], 0.06 [<0.001] million Asian females) but over-represented among ages 85 and older (17% [0.5], 0.01 [<0.001] million Asian males; 25% [0.3], 0.03 [<0.001] million Asian females). The lowest HDI decile for the 25–44 age group was composed primarily of males (76% [<0.1], 6.44 [0.009] million) whereas this decile was predominantly female (71% [0.1], 0.42 [0.002] million) for ages 85 and older. In the highest HDI decile, shifts in the composition of the population by age were particularly large for White males, who made up 5% (0.1, 0.39 [0.001] million) of this decile in age group 25–44, but 49% (0.2, 0.29 [0.001] million) in age group 85 and older. From 2012 to 2021, the proportion of the population living in the lowest HDI decile varied substantially by location, and a disproportionately high share of the population living in locations in much of the southern half of the USA, Appalachia, and rust-belt states were in the lowest HDI decile. For most race and sex groups, mean HDI increased gradually from 2008 to 2019, then declined in 2020 due to declines in expected lifespan. Interpretation Substantial disparities in well-being exist within the USA and are heavily influenced by race (due to racism), sex, age, and geographical location. These disparities are not immutable, but improvement is not a given, and gains can be fleeting in the face of a crisis like the COVID-19 pandemic. Sustained action to ensure that everyone has meaningful access to a high-quality education (including college), the means to earn a sufficient income, and the opportunity live a long and healthy life is needed to reduce these disparities and should focus on the populations and locations that are worst off. Funding State of Washington and National Institute on Minority Health and Health Disparities