Novel duck reovirus (NDRV) causes high morbidity in ducklings, and the recovered individuals often show stunted growth. There is currently no commercial vaccine available for effectively controlling NDRV. The capsid protein σC in NDRV is responsible for virus–cell attachment and thus plays a key role in viral infection. In this study, we aimed to develop a new vaccine candidate presenting σC on the virus-like particle AP205 according to specific binding with SpyCatcher and SpyTag. Firstly, σC-SpyTag was expressed in E. coli and purified, which was then coupled to AP205-SpyCatcher to generate AP205-σC. Then, AP205-σC was characterized, and the results demonstrated that it remained intact and had a homogenous viral particle structure, which packaged prokaryotic ssRNA inside. After immunizing ducklings with it, AP205-σC induced σC-specific IgY antibodies that could effectively recognize NDRV. Importantly, these antibodies were able to block the virus from infecting duck embryo fibroblasts in vitro, suggesting the vaccine successfully elicited neutralizing antibodies in ducklings. Consistently, the clinical pathologic features like lesions or listlessness in the AP205-σC-immunized ducklings were drastically reduced compared to those in the control group. Moreover, the viral loads in the AP205-σC-immunized ducklings were strikingly reduced, indicating that the vaccine contributed to viral clearance. These results suggested that AP205-σC exhibited excellent immunogenicity and posed protection against NDRV infection in ducks. In conclusion, AP205-σC has the potential to induce neutralizing antibody responses against NDRV and is worthwhile to develop for large-scale application.