Highly Pathogenic Avian Influenza H5N1 (HPAI H5N1) was first detected in chickens in Scottland in 1959 and has since circulated globally, causing regular outbreaks among different animal species, as well as incidental infections in humans. In this scoping review, the epidemiology and impact of HPAI H5N1 among migratory birds, poultry, and cattle in the United States were analyzed, with a particular focus on outbreaks since January 2022. Following PRISMA guidelines, a total of 27 articles were identified for this review. Publicly available data and reports from the USDA and CDC were also evaluated and summarized. The identified articles primarily included epidemiological studies of detections in wild birds, mammals, and case reports on H5N1 and transmission dynamics among cattle, with a notable absence of poultry-focused reports. Wild birds, especially migratory species, have played an important role in virus dissemination. Studies among mammals, including seals, bears, and domestic cats, along with the emerging outbreak among cattle, highlight the virus’s ability to adapt to diverse hosts, with the possibility of mammal-to-mammal transmission. Despite the low number of human infections, the zoonotic risk of the disease and the possibility of a human outbreak remain significant. The complexity and risks associated with the virus, in comparison with the limited current scientific studies in the United States, demand further investigations to mitigate its impact on animals, ecosystems, and human health.