Polyploidy or whole genome duplication (WGD) is a prominent feature for genome evolution of some animals and all flowering plants, including many important crops such as wheat, cotton, and canola. In autopolyploids, genome duplication often perturbs dosage regulation on biological networks. In allopolyploids, interspecific hybridization could induce genetic and epigenetic changes, the effects of which could be amplified by genome doubling (ploidy changes). Albeit the importance of genetic changes, some epigenetic changes can be stabilized and transmitted as epialleles into the progeny, which are subject to natural selection, adaptation, and domestication. Here we review recent advances for general and specific roles of epigenetic changes in the evolution of flowering plants and domestication of agricultural crops.