To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.