Abstract Genome-structural evolution on a large scale is prevalent in various organisms. The role of genome-structural rearrangements, including chromosome fusions, has been revealed in genome evolution and species divergence. However, the empirical evidence in adaptation remains debated at the current time. We investigated the phylogenetic relationship, genomic divergence and environmental associations of closely related Asian clams: the freshwater species Corbicula fluminea and brackish-freshwater species Corbicula mortoni. The chromosome-level genome assembly of brackish-freshwater C. mortoni using single-molecule and Hi-C sequencing revealed a chromosome-scale rearrangement relative to freshwater C. fluminea. Strikingly, genomic characterization studies including outgroup species Archivesica marissinica indicated two independent fusion events in these closely related species. Transcriptome analysis under salinity stress identified differentially expressed genes (DEGs) and revealed a significant enrichment of significantly down-regulated genes (SDGs) on the fused chromosome of C. mortoni, suggesting possible regulatory shifts associated with fusion. In summary, our genomic and transcriptomic analyses document important chromosome-scale evolutionary events during Corbicula speciation and provides insights into the relationship between genomic reorganization and gene regulation in response to environmental variation.