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Common wheat (Triticum aestivum L.) is one of the most important crops because it provides about 20% of the total calories for humans. T. aestivum is an excellent modern species for studying concerted evolution of sub-genomes in polyploid species, because of its large chromosome size and three well-known genome donors. Establishment of common wheat genome reference sequence and development of high-density SNP chips provide an excellent foundation to answer questions of wheat evolution and breeding at the genomic level. By genotyping more than 600 accessions of common wheat and their diploid and tetraploid ancestors using a Wheat660K SNP array, we found dramatic genome changes due to tetraploidization and hexaploidization, in contrast to weaker influences of domestication and breeding on them. Further, since common wheat was introduced in China in 1500 BCE, Chinese landraces formed two subgroups (T. aestivum-L1 and T. aestivum-L2) with considerably diverse geographic distributions and agronomic traits. T. aestivum-L2, mainly distributed in central and east China is found to have more but smaller oval grains with early maturity characteristics. We found that variation and selection in intergenic regions of the A and B sub-genomes dominated this differentiation, in which chromosomes 7A and 3B took the leading roles due to the existence of putative genes related to defense responses and environmental adaption in the highly differentiated regions. Large haplotype blocks were detected on 3B (232.6–398.3 Mb) and 7A (211.7–272.9 Mb) in the landraces, forming two distinct haplotypes, respectively. We discovered that artificial crosses in breeding promoted recombination in the whole genome, however, this recombination and differentiation was highly asymmetric among the three sub-genomes in homoeologous regions. In addition, we found that the wide use of European and northern American cultivars in breeding at early era, led dramatic changes in Chinese wheat genome, whereas, the recent breeding functioned to optimize it. This study will provide the insight for reconsideration of wheat evolution and breeding, and a new strategy for parent selection in breeding.