Wheat (Triticum aestivum L.) is one of the most important staple crops. Most of wheat varieties are sensitive to salt stress, which is a major limitation for wheat production. To develop salt-tolerant wheat varieties for sustainable grain production, we used ethylmethylsulfonate to mutagenize over 90,000 seeds of the wheat cultivar Luyuan502. A total of 2000 salt-tolerant lines were identified after screening the plants in a salinized field. We further analyzed ethylene sensitivity, salt related physiological changes, and preliminary crop yield of the selected plants. We found 11 salt-tolerant lines exhibiting ethylene insensitivity and high grain production. Transcriptome analysis revealed 3278 differently expressed genes (DEGs) in the selected mutants, including the ones encoding CABs, PERs/PODs, BGLUs, CYP707s, and ZEPs. Most of DEGs may be involved in photosynthesis, biosynthesis of secondary metabolites, cyanoamino acid metabolism, carotenoid biosynthesis, thiamine metabolism, and cutin, suberine and wax biosynthesis pathways. In addition, 9 novel ETHYLENE RESPONSE FACTORs (ERFs) were identified and analyzed in the mutants. These ERFs may play critical roles in ethylene response and salt tolerance. The mutant lines with decreased ethylene sensitivity exhibited enhanced salt tolerance, suggesting that ethylene sensitivity was closely related with salt tolerance.