Novel H5N6 highly pathogenic avian influenza viruses (HPAIVs) were isolated from duck farms and migratory bird habitats in South Korea in November-December 2017. Genetic analysis demonstrated that at least two genotypes of H5N6 were generated through reassortment between clade 2.3.4.4 H5N8 HPAIVs and Eurasian low pathogenic avian influenza virus in migratory birds in late 2017, suggesting frequent reassortment of clade 2.3.4.4 H5 HPAIVs, and highlighting the need for systematic surveillance in Eurasian breeding grounds.