The growing incidence of H5Ny virus infection in humans and mammals causes an increasing public health concern. To date, H5Ny virus infection in humans and mammals has been reported in 46 countries around the world, and the infection scope is gradually expanding from Southeast Asia to Europe and from Europe to the Americas. Virus subtypes include H5N1, H5N2, H5N5, H5N6 and H5N8, among which H5N1 subtype accounts for more than 95.63% cases. Forty clades have been identified, of which clade 2.3.4.4b accounts for majority of H5Ny mammalian infection cases. From 1997 to 2021, the number of H5Ny mammalian infection cases was low, with a small peak in 2006, and a sharp rise after 2022. The main clades of H5Ny viruses were clade 0 and 1 in 1997–2004, and gradually shifted to clade 2.1.3.2, 2.1.3.2b, 2.2.1, 2.2.1.2, and 2.3.4 from 2005 to 2014, and gradually shifted to 2.3.4.4b, 2.3.4.4e and 2.3.4.4 h after 2015, among which clade 2.3.4.4b became the dominant clade. The H5Ny AIVs from 14 mammal species could be classified into 31 genotypes, including G1–G3, G6–G7, G13, G25–G27 and G31 in cats, G18–G23, G28–G29 and G31 in foxes, G2, G9–G10, G14–G16 and G24 in minks, G1–G2, G4–G5, G8 and G11 in tigers, G21–G22, G29 and G31 in skunks, and G31 in dairy cows. From 2021 to early 2024, there are two main migration patterns: intra-European spread and European spread to North America. The infection of H5Ny AIVs in mammals is hampered by host body temperature, receptor distribution, pH value, and other factors, including ANP32, TUFM, DDX17 and BDN3A3. Comprehensive measures should be taken to prevent and control of H5Ny AIVs infection in mammals, including surveillance, vaccination and biosafety control measures.