Riemerella anatipestifer is an infectious pathogen that causes septicemia and polyserositis in ducks. Our previous studies showed that RA CH-1 ∆fur was significantly attenuated in ducklings, which highlights the potential of this strain as a live attenuated vaccine. In this study, it was shown that infection with 109 CFU of the fur mutant did not cause any clinical symptoms or significant histological lesions in 3-day-old ducklings and that the bacteria were readily cleared by the host within 3 d. Compared with the nonvaccinated group, the group inoculated with the mutant strain RA CH-1 ∆fur exhibited protection of ducklings against a high-dose (2.28 × 1010 CFU) challenge with the wild-type strain RA CH-1. Moreover, the average body weights and body weight gains of the Δfur-inoculated group were not significantly affected by the challenge. Further analysis revealed that RA CH-1 ∆fur elicited higher IgY titers and that the serum antibody levels persisted for at least 49 d after immunization. Overall, our study showed that RA CH-1 ∆fur is a safe and effective vaccine candidate that is expected to play an important role in RA CH-1 infection prevention in the duck industry. https://doi.org/10.1016/j.psj.2022.102450.