Craniofacial malformations arise from developmental defects in the head, face, and neck and account for one third of congenital defects at birth.  Clinical phenotypes such as DiGeorge Syndrome, the most common microdeletion condition, illustrate a developmental link between cardiovascular and craniofacial morphogenesis.  Moreover, recent fate mapping studies in mice and zebrafish support this notion through identification of a multipotent progenitor in the cardiopharyngeal field that gives rise to the heart, branchiomeric muscles, and pharyngeal arch (PA) arteries.  NKX2-5 is a key cardiac transcription factor associated with human congenital heart disease and mouse models of Nkx2-5 deficiency highlight critical roles in cardiac development.  In zebrafish, nkx2.5 and nkx2.7 are paralogous genes in the NK4 family expressed in cardiomyocytes and PAs.  Despite the shared cellular origins of cardiac and craniofacial tissues, the function of NK4 factors in head and neck patterning has not been elucidated.  Here, we demonstrate that Nkx2.7 serves as a previously unappreciated, crucial regulator of craniofacial muscle and cartilage formation.  Our data reveal a unique requirement for nkx2.7 in PA1- and PA2-derived branchiomeric muscle and cartilage elements for which nkx2.5 cannot compensate.  Moreover, molecular evolutionary analysis of NK4 genes reveals that nkx2.5 and nkx2.7 are ohnologs resulting from two rounds of vertebrate whole genome duplications with an early split between them, underscoring the concept that these genes play independent roles during development.  We uncover mechanisms mediated by Nkx2.7 in PA derivatives through identification of a requirement in branchiomeric progenitor proliferation necessary to generate mandibular and hyoid muscles of the lower jaw.  Our data further highlight that Nkx2.7 is critical in patterning the cranial neural crest domains to establish the dorsal and ventral jaw cartilages.  Furthermore, we reveal a critical function for Nkx2.7 in inhibiting Notch signals in the dorsal neural crest to configure cartilage and joint derivatives of ventral region.  Together, our studies shed light on an evolutionarily conserved, unique function of Nkx2.7 in vertebrate craniofacial development and have the potential to advance understanding of the etiologies and therapeutic interventions for patients with congenital deformities of the head and neck.