High pathogenicity avian influenza virus H5N1 subtype (H5N1 HPAIV), clade 2.3.4.4b, is expanding its host and geographical range, and invaded Antarctica in 2023. Although mortality in Antarctic wildlife from H5N1 HPAIV has been suspected, mainly based on virological analysis of swabs collected from dead animals, it has not been unequivocally diagnosed. Here we show that H5N1 HPAIV caused high mortality in a breeding colony of skuas at one of ten sites in Antarctica we visited in March 2024. By combined virological, bacteriological and pathological analyses, we found that H5N1 HPAIV caused multi-organ necrosis and rapid death in skuas, but not in other species examined. Taken together with recent data, skuas in Antarctica are at risk of continued mortality from H5N1 HPAIV infection, threatening their already small populations. Conversely, because of their wide distribution and ecological relevance, skuas may play a substantial role in the spread of the virus across Antarctica. Transdisciplinary surveillance is needed in coming years to monitor the impact of this poultry-origin disease on Antarctica’s unique wildlife.