Abstract Objective The association between segmental body composition and bone mineral density (BMD) remains uncertain. The primary aim of this cross-sectional investigation was to elucidate the connection between segmental body composition and BMD within the United States adult population. Methods We selected a cohort of 10,096 individuals from the National Health and Nutrition Examination Survey (NHANES) database, with a mean age of 39 years and a mean BMI of 28.5 kg/m². The parameter of segmental body composition was achieved by quantifying body fat and lean mass percentages across various anatomical regions, including the torso, Android, Gynoid, arms and legs. We conducted a weighted multivariate linear regression analysis to investigate the association between segmental body composition and total BMD. Additionally, subgroup analysis was performed based on age and gender. Results We found an inverse association between fat proportion in each anatomical region and total BMD, with the arm and leg regions demonstrating the most significant negative correlation. Conversely, a positive correlation was observed between lean mass and BMD across all anatomical regions. These associations remained consistent in subgroup analyses. Conclusion Our investigation revealed a negative association between adipose levels in various anatomical regions and BMD among Americans aged 20 to 59. Importantly, higher fat proportion in the extremities exerted the most deleterious impact on BMD. Furthermore, an increase in lean mass within each anatomical region was ascertained to confer a positive effect on bone health. Consequently, the evaluation of segmental body composition is well-positioned to predict bone health status.