After a decade of no reported human cases, Cambodia faces a resurgence of highly pathogenic avian influenza (HPAI) A(H5N1) virus infections, with an overall mortality of 38%. Cases have occurred primarily in children and adolescents who were exposed to infected poultry. From February 2023 through August 2024, a total of 16 infections were detected through the long-standing national influenza-like illness and severe acute respiratory infection surveillance systems, both of which were strengthened by expanded laboratory-testing capacity that was developed during the coronavirus disease 2019 pandemic. All 16 patients reported exposure to sick or dead poultry, and outbreak investigations identified contemporary, genetically similar viruses in poultry collected in or around case households or from active, longitudinal surveillance of live-bird markets. Genomic sequencing revealed an avian origin for all the human infections, and sequences have been publicly shared through the Global Initiative on Sharing All Influenza Data (also known as GISAID)