Highly pathogenic H5N1 avian influenza is considered an avian disease, although there is some evidence of limited human‐to‐human transmission of the virus. A global effort is underway to control or eradicate the highly pathogenic H5N1 avian influenza virus in poultry and prevent human exposure, both of which may also reduce the risk of pandemic emergence. Hemagglutinin gene sequences from 215 human H5N1 influenza viruses were used to trace the source and dispersal pattern of human H5N1 influenza viruses on a global scale. A mutation network and phylogenetic analyses of the hemagglutinin gene show that human H5N1 influenza viruses can be clearly divided among 4 clusters across geographic space. On the basis of analysis of the N‐glycosylation sites at positions 100 and 170 in the hemagglutinin protein, human H5N1 influenza viruses were also divided into 3 types. When we combined these analyses with geographic information system data analyses, we found that Southern China is often a common source of multiple clusters of H5N1 influenza viruses and that each cluster has different dispersal patterns and individual evolutionary features. In summary, the genetic evidence presented here provides clear evidence for multiple clusters of human H5N1 influenza viruses that initially originated in Southern China.