During winter 2016–17, outbreaks of highly pathogenic avian influenza (HPAI) virus A(H5N8) clade 18.104.22.168b caused substantial losses in wild water birds and domestic poultry across Europe. This virus is related to strains from China and Mongolia and has a high potential for reassortment. Genetic and temporal analysis of these isolates revealed multiple reassortant events, indicating multiple independent entries into Europe; the outbreaks in Germany were dominated by 5 independent reassortant groups of HPAI virus H5N8. Several outbreaks of HPAI virus H5Nx strains in wild birds confirmed the continued presence of H5 clade 22.214.171.124b in Europe well into the summer of 2017. This virus’s high tendency to reassort raised concerns that further reassorted strains could dominate in HPAI outbreaks in Europe or become enzootic in wild bird populations in the future. In this study, we set out to characterize related reassortant viruses of subtype H5N6 or H5N5 isolated in Germany during 2017–2018 and delineate their zoonotic potential in ferrets.