Six highly pathogenic avian influenza (HPAI) H5N1 viruses (clade 2.3.4.4b) were detected in migratory birds in Hubei Province in November 2021. Phylogenetic analysis indicated that the viruses in the study included two different reassortants between H5N1 viruses that were circulating in Eurasia and low-pathogenic avian influenza viruses (LPAIVs). Several amino acid substitutions that contributed to the enhanced replication or virulence in mammals were observed in these viruses, suggesting a potential threat of the H5N1 viruses to human health. IMPORTANCE Here, we obtained the whole-genomes of six H5N1 viruses from dead or rescued wild birds in Hubei Province. These viruses were divided into two genotypes and had different evolutionary trajectories from previously reported H5N1 viruses in China. Extensive reassortment events between high-pathogenic (HP) and low-pathogenic (LP) avian influenza viruses (AIVs) were observed in these viruses. Moreover, a key amino acid analysis also suggests a potential threat of H5N1 viruses to public health. Our work explored the prevalent patterns of H5N1 viruses in wild birds and replenished the viral population data of H5N1 viruses in central China.