Brittlestars in the family Ophiocomidae are large and colourful inhabitants of tropical shallow water habitats across the globe. Here we use targeted capture and next-generation sequencing to generate robust phylogenomic trees for 39 of the 43 species in order to test the monophyly of existing genera. The large genus Ophiocoma, as currently constituted, is paraphyletic on our trees and required revision. Four genera are recognised herein: an expanded Ophiomastix (now including Ophiocoma wendtii, O. occidentalis, O. endeani, O. macroplaca, and Ophiarthrum spp), Ophiocomella (now including the non-fissiparous Ophiocoma pumila, aethiops and valenciae) and Breviturma (now including Ophiocoma pica, O. pusilla, O. paucigranulata and O. longispina) and a restricted Ophiocoma. The resulting junior homonym Ophiomastix elegans is renamed O. brocki. The genus Ophiomastix exhibits relatively high rates of morphological disparity compared to other lineages. Ophiomastix flaccida and O. (formerly Ophiarthrum) pictum have divergent mitochondrial genomes, characterised by gene-order rearrangements, strand recoding, enriched GT base composition, and a corresponding divergence of nuclear mitochondrial protein genes. The new phylogeny indicates that larval and developmental transitions occurred rarely. Larval culture trials show that species with abbreviated lecithotrophic larval development occur only within Ophiomastix, although the possible monophyly of these species is obscured by the rapid early radiation within this genus. Asexual reproduction by fission is limited to one species-complex within Ophiocomella, also characterised by elevated levels of allelic heterozygosity, and which has achieved a relatively rapid global distribution. The crown ages of the new genera considerably predate the closure of the Tethyan seaway and all four are distributed in both the Atlantic and Indo-Pacific Oceans. Two species pairs appear to reflect the closure of the Panama Seaway, although their fossil-calibrated node ages (12–14 ± 6 my), derived from both concatenated sequence and multispecies coalescent analyses, considerably predate the terminal closure event. Ophiocoma erinaceus has crossed the East Pacific barrier and is recorded from Clipperton Island, SW of Mexico.