Objectives. To estimate the number and prevalence of workers in the United States exposed to chemical hazards available in the Canadian job-exposure matrix (CANJEM) database and examine exposure disparities across sociodemographic groups. Methods. We merged US worker demographic data from the Current Population Survey with CANJEM to characterize the burden and sociodemographic distribution of 244 chemical exposures in the United States in 2021. An interactive version of the full data set is available online (https://deohs.washington.edu/us-exposure-burden). Results. Of the chemical exposures examined, the most prevalent were cleaning and antimicrobial agents (14.7% of workforce estimated exposed), engine emissions (12.8%), organic solvents (12.1%), polycyclic aromatic hydrocarbons (10.1%), and diesel engine emissions (8.3%). Racial and ethnic minoritized groups, persons with lower educational attainment, foreign-born noncitizens, and males were generally overrepresented in exposure to work-related chemical hazards. Conclusions. In the United States, marginalized sociodemographic groups are estimated to experience an inequitable burden to many chemical exposures because of occupational segregation. Data from this analysis can inform occupational and public health research, policy, and interventions aimed at reducing the burden of disease and health inequities in the United States. (Am J Public Health. 2024;114(1):57-67. https://doi.org/10.2105/AJPH.2023.307461).