A new species of stream-dwelling crayfish, Cambarus franklini, the South Mountains crayfish, is described from the upper South Fork Catawba River basin in western North Carolina, USA using morphological and genetic data. Cambarus franklini was previously considered a member of the widespread and morphologically variable Cambarus species C complex and is morphologically most similar to an undiagnosed member of the group native to the upper Catawba River basin in NC. Cambarus franklini can be differentiated from this species group by several morphological characteristics including: lacking a well-defined double row of tubercles along the mesial margin of the palm, possessing a more weakly convergent and longer acumen, and conspicuous blue-green and red coloration, particularly throughout the telson and along the distal margins of the rami. This species is phylogenetically most similar to Cambarus johni, Cooper, 2006, another former member of the Cambarus species C group. Cambarus franklini has a limited geographic range (<100 km2) and is currently known only from the Henry and Jacob Fork watersheds in the South Mountains region of the Eastern Blue Ridge foothills.