Wheat is one of the most important staple crops worldwide. However, salt stress caused by soil salinization severely constrains its stable yield and productivity. Conventional approaches for ameliorating saline–alkali soils, including physical, chemical, and biological strategies, are generally limited by high costs, poor stability, and susceptibility to environmental fluctuations. Therefore, enhancingsalt tolerance in wheat represents the most effective and direct approach to cope with salinized lands. In this study, 154 wheat accessions endemic to Xinjiang, China, were evaluated for salt tolerance at both germination and seedling stages under simulated salt stress with 256 mmol·L?¹ NaCl. Based on the phenotypic evaluation, contrasting accessions were selected for subsequent transcriptome profiling. The results showed that salt stress significantly inhibited seed germination potential, germination rate, and seedling growth vigor, with substantial variations in salt tolerance observed among accessions at both developmental stages. A total of 23 tolerant and 35 sensitive accessions were identified. Comparative GO and KEGG enrichment analyses of differentially expressed genes (DEGs) between the tolerant cultivar ''Xindong 40'' and the sensitive cultivar ''Xindong 48'' revealed distinct transcriptional strategies. In ''Xindong 40'', up-regulated DEGs were mainly enriched in ABA signaling, redox homeostasis maintenance, and flavonoid biosynthesis, whereas down-regulated DEGs were associated with auxin response and basal energy metabolism, suggesting a coordinated stress response involving activation of defense signaling and protective metabolism alongside suppression of growth-related processes. In contrast, up-regulated DEGs in ''Xindong 48'' were predominantly linked to membrane transport and antioxidant metabolism, while key pathways including photosynthesis, carbon/nitrogen fixation, and brassinosteroid biosynthesis were down-regulated, indicating impaired photosystem function and disrupted energy homeostasis. Integrated analysis of DEGs and enrichment results further identified key salt-responsive candidate genes, including SOS(TraesCS1B02G370900) and HKT (TraesCS7B02G318800, TraesCS7D02G411300) family members. Collectively, this study provides important theoretical insights and genetic resources for dissecting the molecular mechanisms underlying salt tolerance in wheat, facilitating the discovery of salt-tolerance genes and the breeding of novel tolerant varieties.