The relationship between A body shape index (ABSI) and osteoarthritis (OA) remains unclear, particularly regarding sex- and age-related differences. This study aimed to investigate the association between ABSI and OA, as well as its sex-specific and age-related variations. Data from 39,095 U.S. adults in the 1999 to 2020 National Health and Nutrition Examination Survey (NHANES) database were analyzed, with an OA prevalence of 11.50%. ABSI was calculated using the formula: WC (m)/ [BMI (kg/m 2 ) 2/3 × Height (m) 1/2 ]. A weighted multivariate-adjusted logistic regression model revealed a significant positive correlation between ABSI and OA: each 0.01 increase in ABSI was associated with a 13% higher risk of OA (OR: 1.13; 95% CI: 1.03, 1.23). Compared with the lowest ABSI quartile, the highest quartile showed a 24% increased risk of OA (OR: 1.24; 95% CI: 1.05, 1.46). Subgroup analyses showed consistent associations between the various interaction responses, but with variations by sex, age, race, and diabetes status. Notably, the association was more pronounced in men and young-to-middle-aged adults (OR for young and middle-aged: 1.17; 95% CI: 1.03, 1.34; OR for men: 1.32; 95% CI: 1.15, 1.53) but not statistically significant in women or older adults. These findings suggest that higher ABSI (especially abdominal obesity) predicts an increased risk of OA in men and young-to-middle-aged populations, warranting targeted interventions. Future studies should use ABSI as a body size assessment tool to explore underlying mechanisms.