Abstract Hox genes play a central role in neural crest (NC) patterning particularly in the cranial region of the body. Despite evidence that simultaneous loss of Hoxa1 and Hoxb1 function resulted in NC specification defects, the role of Hox genes in NC specification has remained unclear due to extended genetic redundancy among Hox genes. To circumvent this problem, we expressed anterior Hox genes in the trunk neural tube of the developing chick embryo. This demonstrated that anterior Hox genes play a central role in NC cell specification by rapidly inducing the key transcription factors Snail2 and Msx1/2 and a neural progenitor to NC cell fate switch characterized by cell adhesion changes and an epithelial-to-mesenchymal transition (EMT). Cells delaminated from dorsal and medial neural tube levels and generated ectopic neurons, glia progenitors, and melanocytes. The mobilization of the NC genetic cascade was dependent upon bone morphogenetic protein signaling and optimal levels of Notch signaling. Therefore, anterior Hox patterning genes participate in NC specification and EMT by interacting with NC-inducing signaling pathways and regulating the expression of key genes involved in these processes.