Subclade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses, emerged in 2013 with multiple subtypes of H5N8, H5N1, and H5N6, had unprecedently caused a global epizootic by H5N1 since 2021, which had devasted multiple species of wild birds, poultry, and wild mammals (terrestrial and marine) with a high mortality, causing severe ecological damage. The infected wild mammals may become new “mixers” for influenza viruses, posing the potential transmission to human. Frequent outbreaks of subclade 2.3.4.4b H5Nx viruses among wild birds and poultry had exposed major gaps in our knowledge on their evolution, spatiotemporal diffusion, and species-crossing transmission. Here, we integrated the phylogenetic and epidemiological data of subclade 2.3.4.4b H5Nx viruses in public database and used Bayesian phylodynamic analysis to reveal the pattern of the global large-scale transmission. Phylogenic analysis demonstrated that the HA gene of these viruses diverged into two dominant clusters around 2015 and 2016. The Bayesian phylodynamic analysis illustrated that the viruses presented spatiotemporally complex transmission network with geographical and host relative expansion and recombination with different subtypes of NA segment. Spatially, the Russian Federation (Siberia) was identified as the primary hub for virus transmission, which was further facilitated by the establishment of strong epidemiological linkages between West Europe and broader regions, such as North America. As for hosts, wild Anseriformes were the primary species for the virus spillover, contributing to the spatial expansion and rapid diffusion globally of subclade 2.3.4.4b viruses. We investigated the phylogeny of subclade 2.3.4.4b H5Nx viruses and the spatiotemporal pattern of transmission with initial location and the primary host, which could provide comprehensive insights for subclade 2.3.4.4b H5Nx viruses. Due to the wild birds involved the widespread of subclade 2.3.4.4b H5Nx viruses, the epizootics in poultry are inevitable, so we highly recommend to apply the policy of culling plus with vaccination to protect the poultry industry and potentially protect the public health.