We use a powerful model Arabidopsis suecica (TTAA), an allotetraploid formed between A. thaliana (TT) and A. arenosa (AA), to reveal genomic and epigenomic contributions to stability in resynthesized and natural allotetraploids. These genomic and epigenomic diversifications may reconcile intergenomic incompatibility and improve stability and adaptation during polyploid evolution.