Salinity is one of the main abiotic stresses limiting crop productivity. In the current study, the transcriptome of wheat leaves in an Iranian salt-tolerant cultivar (Arg) was investigated in response to salinity stress to identify salinity stress-responsive genes and mechanisms. More than 114 million reads were generated from leaf tissues by the Illumina HiSeq 2500 platform. An amount of 81.9% to 85.7% of reads could be mapped to the wheat reference genome for different samples. The data analysis led to the identification of 98819 genes, including 26700 novel transcripts. A total of 4290 differentially expressed genes (DEGs) were recognized, comprising 2346 up-regulated genes and 1944 down-regulated genes. Clustering of the DEGs utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that transcripts associated with phenylpropanoid biosynthesis, transporters, transcription factors, hormone signal transduction, glycosyltransferases, exosome, and MAPK signaling might be involved in salt tolerance. The expression patterns of nine DEGs were investigated by quantitative real-time PCR in Arg and Moghan3 as the salt-tolerant and susceptible cultivars, respectively. The obtained results were consistent with changes in transcript abundance found by RNA-sequencing in the tolerant cultivar. The results presented here could be utilized for salt tolerance enhancement in wheat through genetic engineering or molecular breeding.