Objective Anti-integrin αvβ6 autoantibodies (anti-αvβ6) have recently been described as informative biomarkers for ulcerative colitis (UC), demonstrating a high sensitivity and specificity compared to patients without inflammatory bowel disease (IBD). Given the association between axial spondyloarthritis (axSpA) and IBD, we sought to evaluate the potential of anti-αvβ6 as a biomarker in axSpA patients with or without concurrent IBD. Methods Using an established ELISA protocol, we measured anti-αvβ6 levels in sera of patients with (1) axSpA and UC, (2) axSpA and Crohn disease (CD), (3) axSpA alone, and (4) healthy controls (HCs). Anti-αvβ6 absorbance values were compared between patient groups and clinical variables were compared with anti-αvβ6 positivity. Results Eighteen patients with axSpA and UC, 29 with CD, 48 with axSpA alone, and 48 HCs were included. Patients with axSpA and UC showed a significant increase in mean absorbance and anti-αvβ6 positivity rate compared with axSpA alone. For the diagnosis of UC among patients with axSpA, anti-αvβ6 had a sensitivity of 55.6% and specificity of 89.6%, and receiver-operating characteristic analysis yielded an area under the curve value of 0.83. Anti-αvβ6 positivity was associated with a family history of IBD in patients with axSpA and UC. Surprisingly, anti-αvβ6–positive patients had decreased mean C-reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores compared with anti-αvβ6–negative patients. Examining serial samples, we observed that 3 of 10 anti-αvβ6–positive patients became anti-αvβ6–negative, whereas anti-αvβ6–negative to anti-αvβ6–positive transitions were not observed. Conclusion Anti-αvβ6 positivity demonstrated potential as a diagnostic test for UC in patients with axSpA, particularly those with a family history of IBD. To our knowledge, this is the first study to date examining anti-αvβ6 in axSpA.