Objective The association between segmental body composition and bone mineral density (BMD) is unclear. This study analyzed the representative adult sample from the US in order to evaluate the association between segmental body composition and BMD. Method Ten thousand and ninety-six people aged 20–59 from the National Health and Nutrition Examination Survey (NHANES) database participated in this cross-sectional study. Segmental body composition and total BMD were examined using weighted multivariate linear regression analysis. Additionally, a subgroup analysis was performed according to age and gender group. Result The fat proportion of each body region was negatively related to total BMD once confounding variables were taken into account, while the arm and leg showing the most significant negative correlation. Lean mass and BMD were positively correlated in each region. Similar results were observed in all hierarchical analyses. Conclusion In essence, we discovered that BMD in American individuals aged 20 to 59 was inversely linked with the percentage of fat mass in various body locations. The increase of lean mass in each region had a protective effect on bones. Segmental body composition analysis may be used to provide information for predicting the health status of bone.