In Mexico, the number of cases of the highly virulent Newcastle disease virus is increasing. In 2005, an outbreak of Newcastle disease occurred on an egg laying hen farm in the state of Puebla despite vaccination with the LaSota strain. Farmers experienced a major drop in egg production as a consequence of a field challenge virus. In this study, we characterize the virus, APMV1/chicken/Mexico/P05/2005, responsible for the outbreak. The virus is categorized as a velogenic virus with an intracranial pathogenicity index of 1.99 and a chicken embryo mean death time of 36 h. The complete genome length of the virus was sequenced as consisting of 15,192 bp. In addition, phylogenetic analysis classified the virus as a member of the class II, genotype V. The highly pathogenic nature of the virus has been linked to the amino acid sequence at the fusion protein cleavage site, which contains multiple basic amino acids (RRQKR↓F).