Mortalities in Black Vultures (Coragyps atratus) caused by A/goose/Guangdong/1/1996 2.3.4.4b lineage highly pathogenic (HP) influenza A virus (IAV) H5N1 (HP H5N1) were detected in Florida, USA, on 14 February 2022. By the end of 2022, at least 2,674 and 5,707 deaths where HP H5N1 infection was confirmed or suspected had been documented in Florida and the USA as a whole, respectively. Reported vulture mortalities at die-off locations nationwide ranged from 1 to 700. In Florida and Pennsylvania, USA, antibodies to both H5 and N1 subtypes of IAV were detected in apparently healthy Black Vultures sampled ≤12 mo after mortality events. Antibodies to these subtypes were not detected in Black Vultures at sites in Kentucky and Tennessee, USA, where HP H5N1 was not detected, nor in Pennsylvania vultures sampled before HP H5N1 introduction into North America. Infections in vultures probably originated through scavenging of infected bird carcasses, but once in the vulture population, HP H5N1 infections may have been maintained by conspecific scavenging. Black Vultures can serve as an indicator species for HP H5N1 in North America, and they may sustain an outbreak after infection rates have declined in other species.