An outbreak of highly pathogenic avian influenza (HPAI) led to heavy losses of poultry in commercial farms in North America in 2014–15. Enhanced surveillance by virologists and pathologists at the US Geological Survey National Wildlife Health Center and its partners resulted in the identification of lethal infections with clade 2.3.4.4 subgroup icA2 H5N8 and novel reassortant H5N2 viruses in diverse wild raptor species that died concomitant with the poultry epizootic in the US. A range of pathologic abnormalities were present in dead raptors, including necrotizing encephalitis and myocarditis, pancreatic necrosis, and pulmonary congestion and edema. Raptors are highly susceptible to disease caused by infection with HPAI clade 2.3.4.4 viruses.