A Eurasian strain of H5N1 highly pathogenic avian influenza virus (HPAIV) was first detected in North America in December 2021 and has since been confirmed in numerous wild and domestic avian species. In April 2022, 41 Wild Turkeys (Meleagris gallopavo) were found dead in Johnson County, Wyoming, USA adjacent to a property with confirmed HPAIV in a backyard poultry flock. Oropharyngeal swabs were collected from 11 of the 41 turkeys and necropsy was performed on seven. Avian influenza virus RNA was detected in all 11 turkeys by real-time reverse-transcription PCR. Acute, multiorgan necrosis was observed grossly and identified in all seven turkeys evaluated by histopathology, most consistently in the lung, spleen, liver, gastrointestinal tract, and gonads. Lesions indicate high virulence of subclade 2.3.4.4b H5N1 HPAIV in Wild Turkeys, with infections presenting as clusters of acute mortality. Although documented cases of HPAIV in Wild Turkeys are rare, these findings signify a risk of spillback from domestic poultry, which may be heightened by the recent rise in backyard poultry ownership and the use of peridomestic habitat by wild birds. Additional research is needed to better understand the risk of disease transmission at the interface of Wild Turkeys and backyard poultry and the potential conservation and management implications of HPAIV in wild gallinaceous birds.