Wild birds are the natural reservoirs of Influenza A viruses (IAVs) which cause occasional pandemics and seasonal epidemics. Avian IAVs can be transmitted from wild birds to domestic poultry, low mammals, and humans. It is well accepted that avian IAVs prefer to sialic acids (Sia) α2,3-linked galactose (SAα2,3-Gal), whereas human IAVs to α2,6-linked galactose (SAα2,6-Gal). However, SAα2,3-Gal in wild bird tissues is widely distributed with little variation while some subtypes of avian IAVs have species preference. The different isolation rates among wild bird species cannot be explained by avian IAVs binding to SAα2,3-Gal alone. Specifically, this dissertation had the following aims: Firstly, to determine distribution of glycan receptors across respiratory and gastrointestinal tissues of wild birds and domestic poultry; Secondly, to determine the viral-receptor binding specificity of avian IAVs; Thirdly, to understand the role of glycan motifs in shaping virus evolution during the natural history of IAVs, especially from wild bird to poultry transmission. We found that avian H7 and H10 viruses acquired the binding ability to SAα2,6-Gal without adaptation, furthermore, we evaluated one of these H10 virus that possess the ability of binding to SAα2,6-Gal in ferret model and found it could cause aerosol and contact transmissions. On the other hand, H7 viruses have strong binding avidity to SLex which are present widely in epithelial cells of chicken trachea, which could facilitate the transmission of avian H7 viruses from waterfowl to poultry. Lastly, we found that H7 viruses from waterfowl bound both Neu5Ac and Neu5Gc while chicken isolates from China only prefer to Neu5Ac. Of interest, we found Neu5Gc was found in mallards but not in chickens, which indicated that viruses reduce or lost binding ability to Neu5Gc by adapting in chicken. In summary, this dissertation focused on certain subtypes of avian IAVs, which have caused threats to domestic poultry and public health, and primary avian species for influenza risk. The glycan substructures may play an important role in avian IAVs transmission and adaptation. The knowledge derived from this dissertation will help identify species for influenza surveillance in wild birds and facilitate risk assessment of avian IAVs.