Hexaploid bread wheat (Triticum aestivum L., genome BBAADD) is generally more salt tolerant than its tetraploid wheat progenitor (Triticum turgidum L.). However, little is known about the physiological basis of this trait or about the relative contributions of allohexaploidization and subsequent evolutionary genetic changes on the trait development. Here, we compared the salt tolerance of a synthetic allohexaploid wheat (neo-6 x) with its tetraploid (T. turgidum ; BBAA) and diploid (Aegilops tauschii; DD) parents, as well as a natural hexaploid bread wheat (nat-6 x). We studied 92 morphophysiological traits and analyzed homeologous gene expression of a major salt-tolerance gene High-Affinity K ⁺ Transporter 1;5 (HKT1;5). We observed that under salt stress, neo-6 x exhibited higher fitness than both of its parental genotypes due to inheritance of favorable traits like higher germination rate from the 4 x parent and the stronger root Na ⁺ retention capacity from the 2 x parent. Moreover, expression of the D-subgenome HKT1;5 homeolog, which is responsible for Na ⁺ removal from the xylem vessels, showed an immediate transcriptional reprogramming following allohexaploidization, i.e., from constitutive high basal expression in Ae. tauschii (2 x) to salt-induced expression in neo-6 x . This phenomenon was also witnessed in the nat-6 x . An integrated analysis of 92 traits showed that, under salt-stress conditions, neo-6 x resembled more closely the 2 x than the 4 x parent, suggesting that the salt stress induces enhanced expressivity of the D-subgenome homeologs in the synthetic hexaploid wheat. Collectively, the results suggest that condition-dependent functionalization of the subgenomes might have contributed to the wide-ranging adaptability of natural hexaploid wheat.