Objective <p>The concept of the gut-joint axis is often mentioned when exploring the pathogenesis of Ankylosing spondylitis (AS). This study aims to explore whether there is a causal association between Celiac disease (CeD) and AS.</p> Method <p>Two-sample Mendelian randomization (MR) analysis was conducted using the CeD dataset (the largest pure CeD phenotype dataset in the IEU OpenGWAS database at the time of data retrieval, <i>n</i> = 24,269) and the AS dataset (strictly defined, from the IEU OpenGWAS database, <i>n</i> = 218,030). Inverse Variance Weighting (IVW) was adopted as the primary MR analysis method, supplemented by Weighted Median Estimator, MR-Egger regression, Simple Mode, and Weighted Mode to comprehensively evaluate the causal association between CeD and AS. Additionally, horizontal pleiotropy, heterogeneity, and leave-one-out analysis were performed to further evaluate the robustness and reliability of the results.</p> Results <p>IVW analysis showed a positive causal effect of genetically predicted CeD on AS (OR: 1.435, 95% CI: 1.210–1.702, <i>p</i> = 3.34E-05), and the other four analytical methods also yielded consistent causal effect evaluation results. No significant horizontal pleiotropy or heterogeneity was observed in this study.</p> Conclusion <p>MR analysis indicates that CeD may be a potential risk factor for AS, providing genetic evidence for the increased risk of AS in individuals with a genetic predisposition to CeD.</p>