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Emergence of D1.1 reassortant H5N1 avian influenza viruses in North America Since 2021, highly pathogenic avian influenza viruses (HPAIV) belonging to H5N1 clade 2.3.4.4b have caused high mortality in North American wild birds and poultry. In 2025, a new D1.1 genotype caused two human deaths and host-switched to dairy cattle. However, the evolutionary origins and dynamics of D1.1 have not been fully characterized. Here, our phylogenetic analysis of 17,516 H5N1 genome sequences uncovers how D1.1 introduced a major shift in the antigenic diversity and ecology of the H5N1 epizootic in North America. D1.1 is the first major H5N1 genotype to (a) emerge in the Pacific flyway and spread west-to-east faster than any prior genotype; (b) antigenically shift via reassortment with the North American N1 segment, displacing the previously fixed Eurasian N1; and (c) transmit to a broader range of host species than any H5N1 genotype to date, introducing mammalian adaptations. ### Competing Interest Statement The authors have declared no competing interest. Research Foundation - Flanders, https://ror.org/03qtxy027, G098321N, G0E1420N European Union Horizon 2023 RIA project LEAPS, 101094685 DURABLE EU4Health project 02/2023-01/2027, 101102733 Fonds National de la Recherche Scientifique, F.4515.22 European Union Horizon 2020 project MOOD, 874850 https://www.biorxiv.org/content/10.64898/2025.12.19.695329v1