Halophytes possess inherent stress resilience and diverse adaptations, making them valuable genetic reservoirs for crop breeding. The leguminous halophyte Sesbania bispinosa is a valuable forage crop that thrives in saline soils. To explore its salt tolerance, high-quality genome assemblies is generated for the salt-tolerant S. bispinosa accession SbTA02 and the salt-sensitive accession SbSA44. Genomic analysis revealed that the genomic divergence between the two accessions primarily originates from their pericentromeric and centromeric regions, which contain the two largest inversions: a >27-Mb inversion on chromosome 5 and a ≈49-Mb inversion on chromosome 6. Population-level analysis revealed that the 27-Mb inversion is widespread in S. bispinosa, dividing the tested populations into inland and coastal groups. These groups have many genetic divergence regions (GDRs), with genetically isolated haplotypes in the middle section of chromosome 5, including the large inversion and centromeric regions. Genome-wide association studies (GWAS) identified significant salt-tolerance signals in the GDRs, pinpointing the anthocyanidin synthase gene SbANS. Natural variation in SbANS is associated with differences in salt tolerance between salt-tolerant and salt-sensitive S. bispinosa accessions. These findings provide insights into the genomic evolution of the Sesbania genus and shed light on how genomic variation shapes genome architecture, genetic divergence, and phenotypic differentiation.