BACKGROUND: The weight-to-waist index (WWI) serves as an innovative metric specifically designed to assess central obesity. However, the relationship between WWI and the prevalence of post-stroke depression (PSD) remains inadequately explored in the literature. AIM: To elucidate the relationship between WWI and PSD. METHODS: Data from the National Health and Nutrition Examination Survey 2005 to 2018 were analyzed. Multivariable logistic regression models and propensity score matching were utilized to investigate the association between WWI and PSD, with adjustments for potential confounders. The restricted cubic spline statistical method was applied to explore non-linear associations. RESULTS: Participants with elevated WWI values had a significantly greater risk of developing PSD. Specifically, individuals in the higher WWI range exhibited more than twice the likelihood of developing PSD compared to those with lower WWI values (odds ratio = 2.21, 95% confidence interval: 1.84-2.66, CONCLUSION: There is a significant association between elevated WWI and increased risk of PSD. Thus, regular depression screening should be implemented in stroke patients with elevated WWI to enhance patient outcomes.