Isoxys is a cosmopolitan bivalved arthropod genus known almost exclusively from Cambrian Konservat-Lagerstätten. Despite its wide geographical distribution in such sites of exceptional preservation, little was known of its soft-part anatomy until recently when remains of eyes and raptorial frontal appendages were discovered. This absence has precluded determination of affinities. The new discovery of soft parts led to two important hypotheses: (1) that Isoxys was related to the ‘great-appendage’ arthropods and (2) that its contained species were not congeneric. Neither has been tested using a detailed cladistics analysis. The morphology of Isoxys is re-evaluated and coded into an extensive cladistics analysis. Our results indicate that Isoxys was indeed a monophyletic genus with all representatives united by the presence of an expansive dorsal shield with prominent antero- and posterolateral cardinal spines. It also indicates that Isoxys occupies a crucial role in arthropod evolution, resolving at the base of Arthropoda. The ‘great appendages’ of Isoxys are interpreted as innovating from either the protocerebral or deutocerebral somite and are therefore not homologous to those of other ‘great-appendage’ arthropods, which are interpreted as originating from the tritocerebral somite of the head.