During the winter of 2022/2023, Japan experienced its largest outbreak of high pathogenicity avian influenza (HPAI), affecting 84 poultry premises. In this study, we investigated the pathogenicity and antigenicity of A/chicken/Kagoshima/22A1T/2022 (Kagoshima/22A1T), a clade 2.3.4.4b H5N1 virus belonging to the G2b group. It was isolated from a poultry farm in Izumi City, where the largest number of consecutive cases was recorded. The 50% lethal dose, mean death time (MDT), amount of virus shed, and transmissibility in chickens of Kagoshima/22A1T were similar to those of A/chicken/Kagoshima/21A6T/2022 (Kagoshima/21A6T), the previous season’s isolate of the same group, indicating that their pathogenicities were comparable. However, the antigenicity of these isolates differed according to the hemagglutination inhibition (HI) test results. We found that the amino acid substitutions in residues 189 and 193, corresponding to antigenic site B in the H3 virus of the HA1 subunit, could have an impact on the HI cross-reactivity of Kagoshima/21A6T. This study provides important insights into the factors contributing to the consecutive HPAI outbreaks on poultry farms in Izumi City during the 2022/2023 season and the prediction of antigenic changes in G2b group HPAI viruses.