Bread wheat (Triticum aestivum L.) is one of the most important agricultural plants wearing abiotic stresses, such as water deficit and cold, that cause its productivity reduction. Since resistance to abiotic factors is a multigenic trait, therefore modern genome-wide approaches can help to involve various genetic material in breeding. One technique is full transcriptome analysis that reveals groups of stress response genes serving marker-assisted selection markers. Comparing transcriptome profiles of the same genetic material under several stresses is essential and makes the whole picture. Here, we addressed this by studying the transcriptomic response to water deficit and cold stress for two evolutionarily distant bread wheat varieties: stress-resistant cv. Saratovskaya 29 (S29) and stress-sensitive cv. Yanetzkis Probat (YP). For the first time, transcriptomes for these cultivars grown under abiotic stress conditions were obtained using Illumina based MACE technology. We identified groups of genes involved in response to cold and water deficiency stresses, including responses to each stress factor and both factors simultaneously that may be candidates for resistance genes. We discovered a core group of genes that have a similar pattern of stress-induced expression changes. The particular expression pattern was revealed not only for the studied varieties but also for the published transcriptomic data on cv. Jing 411 and cv. Fielder. Comparative transcriptome profiling of cv. S29 and cv. YP in response to water deficit and cold stress confirmed the hypothesis that stress-induced expression change is unequal within a homeologous gene group. As a rule, at least one changed significantly while the others had a relatively lower expression. Also, we found several SNPs distributed throughout the genomes of cv. S29 and cv. YP and distinguished the studied varieties from each other and the reference cv. Chinese Spring. Our results provide new data for genomics-assisted breeding of stress-tolerant wheat cultivars.