Abstract Background: The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer is not established. Methods: We conducted a nested case–control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States. Results: Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk. Conclusions: Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer. Impact: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples.