Background: Depression has become a multifaceted global health issue, with complex connections to obesity. Weight-adjusted-waist index (WWI) can effectively evaluate central obesity, but the relationship between WWI and depression has not been well studied. The study aims to investigate the potential correlation between these two health parameters., Methods: According to the data from National Health and Nutrition Examination Survey, this cross-sectional study used multiple regression analysis, subgroup analysis, and smooth curve fitting to explore the relationship between WWI and depression. The assessment ability of WWI was evaluated and compared to other obesity indicators using the receiver operating characteristic (ROC) curve., Results: This study analyzed 38,154 participants. Higher WWI is associated with higher depression scores (β = 0.41; 95% CI, 0.36-0.47). After adjusting for various confounding factors, the positive correlation between WWI and depression remained significant (P for trend < 0.0001). Nonlinear positive correlation was detected with a breakpoint of 11.14. ROC analysis shows that compared to other obesity indicators (ROCWWI = 0.593; ROCBMI = 0.584; and ROCWC = 0.581), the correlation between WWI and depression has better discrimination and accuracy. DII mediated 4.93%, SII mediated 5.08%, and sedentary mediated 0.35% of the total association between WWI and depression., Conclusion: WWI levels were related to an increased likelihood of depression and showed a stronger relationship than BMI and waist circumference. Our findings indicated that WWI may serve as a simple anthropometric index to evaluate depression.