Michael II Asen was the son of Ivan Asen II and Irene Komnene Doukaina. He succeeded his half-brother, Kaliman I Asen. His mother or other relative must have ruled Bulgaria during his minority.

John III Doukas Vatatzes, Emperor of Nicaea, and Michael II of Epirus invaded Bulgaria shortly after Michael's ascension. Vatatzes captured the Bulgarian fortresses along the river Vardar; Michael of Epirus took possession of western Macedonia. In alliance with the Republic of Ragusa, Michael II Asen broke into Serbia in 1254, but he could not occupy Serbian territories. After Vatatzes died, he reconquered most territories lost to Nicea, but Vatatzes's son and successor, Theodore II Laskaris, launched a successful counter-offensive, forcing Michael to sign a peace treaty. Shortly after the treaty, discontented boyars (noblemen) murdered Michael.