Aims <p>The huge and complex genome of bread wheat (AABBDD, 2<i>n</i> = 6<i>x</i> = 42) results in gene family expansion, thereby characterizing the core member is indispensable for deciphering the molecular basis of differential salt tolerance between genotypes, further for breeding salt-resilient varieties.</p> Methods <p>In this study, we compared physiological, ionomic, genomic, and transcriptomic landscapes of two allohexaploid wheat accessions, salt-tolerant (H467) and salt-sensitive (L735), under 200&#xa0;mM NaCl stress.</p> Results <p>H467 retained more Na⁺ in roots and accumulated less Na⁺ in shoots than L735, which maintaining weaker photosynthetic efficiency and chloroplast integrity. Salt-tolerant H467 and sensitive L735 exhibit pronounced structural genomic divergence, including millions of SNPs and InDels predominantly in intergenic regions, as well as numerous structural variants and copy number variations, which likely underlie their contrasting responses to salt stress. Transcriptome analysis revealed that <i>TaHKT8-4D</i>, a plasma membrane-localized Na⁺ transporter, was specifically and strongly induced in roots of H467 under salt stress. Co-expression gene network analysis placed <i>TaHKT8-4D</i> in a module negatively correlated with shoot Na⁺ content. Heterologous expression demonstrated that TaHKT8-4D possesses Na⁺ transport activity, leading to Na⁺ overaccumulation and growth inhibition of yeast cells under salt stress. In contrast, L735 showed upregulation of chlorophyll degradation and senescence-associated genes, correlating with severe leaf chlorosis and photosystem II impairment.</p> Conclusions <p>Our findings uncover a mechanism where root-specific induction of <i>TaHKT8-4D</i> restricts Na⁺ translocation to shoots, thereby protecting photosynthetic tissues from ion toxicity and premature senescence, making it a promising candidate for genetic improvement of salt tolerance in wheat breeding programs.</p>