Bivalvesare species-rich mollusks with prominent protective roles in coastal ecosystems. Across these ancient lineages, colony-founding larvae anchor themselves either by byssus production or by cementedattachment. The latter mode of sessile life is strongly molded by left-rightshell asymmetryduring larval development ofOstreoida oysterssuch asCrassostrea hongkongensis. Here, we sequenced the genome ofC. hongkongensisin high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry. Importantly, loss of the homeobox geneAntennapedia(Antp) and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves. Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetricalC. hongkongensisand symmetricalPinctada fucatain their expression profiles. Especially, a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated, and may cooperatively govern asymmetrical shell formation in Ostreoida oysters.