Sox genes specify cell identity in many animal lineages. The sea anemone Nematostella vectensis, has a diverse repertoire of Sox genes, including orthologs of nearly every Sox subgroup found in bilaterian taxa. With few exceptions, the functions of these Sox genes are not known in cnidarians. Using CRISPR/Cas9-mediated genome editing, we show that knockout of NvSox2 causes a homeotic transformation of one type of cnidocyte (stinging cell) into another in N. vectensis. In NvSox2 knockout animals, the small penetrant cnidocytes found in the body wall of the polyp (basitrichous isorhizas) were completely transformed into robust spirocytes, an adherent type of cnidocyte. Knockdown of NvSox2 also resulted in downregulation of cnidocyte-specific transcription factor PaxA in the body wall only; large PaxA-expressing basitrichous isorhizas in the tentacles were unaffected in NvSox2 mutant polyps. Our phylogenetic analysis of Sox genes from a broad sample of cnidarian and bilaterian taxa suggests that NvSox2 is a SoxD ortholog. As SoxD genes are known to regulate differentiation of neuronal subtypes across bilaterians, our results suggest this homeotic function of SoxD genes may have arisen before cnidarians and bilaterians diverged from their common ancestor. Robust spirocytes are common in many species of sea anemone but have not been reported previously from N. vectensis. We suggest the role of NvSox2 in driving transformation of an adherent cnidocyte into a penetrant cnidocyte was a key regulatory change that promoted the evolutionary transition from an attached to a burrowing lifestyle in N. vectensis.