Background <p>Obesity is considered an important risk factor for osteoarthritis (OA), with conicity index (C-index), relative fat mass (RFM) are two novel anthropometric measures of obesity. To investigate the association between OA and these two indicators, we conducted this study.</p> Methods <p>We used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the association between C-index, RFM, and OA. First, the participants were divided into two groups according to whether they had OA, and we compared the baseline characteristics of the two groups. Then, C-index and RFM were divided into quartiles (Q1, Q2, Q3, Q4) for multivariate regression analysis. Additionally, we applied restricted cubic spline (RCS) to assess whether the relationship is non-linear. Finally, we conducted a subgroup interaction analysis to investigate whether this relationship varies across different subgroups.</p> Results <p>The study included 34,707 participants, with a weighted OA prevalence of 7.7%. Significant differences in C-index and RFM were observed between OA and non-OA groups. Treating C-index and RFM as categorical variables, logistic regression showed significantly higher OA risk in Q4 compared to Q1: for C-index, Q4 (OR = 1.60; 95% CI: 1.33–1.93; <i>P</i> &lt; 0.001); for RFM, Q4 (OR = 2.07; 95% CI: 1.57–2.73; <i>P</i> &lt; 0.001). The RCS results show that the relationship between C-index and OA is non-linear, while the relationship between RFM and OA is linear. Subgroup interaction analysis showed some interaction effects.</p> Conclusions <p>This study reveals detailed relationships between C-index, RFM, and OA, which may be better indicators of obesity in assessing OA risk.</p>