Mitso Asen became emperor of Bulgaria after the murder of his wife's cousin, Kaliman Asen II in 1256. Although he acquired some support in the capital Tărnovo and in Preslav, he was faced by the hostility of much of the provincial nobility. Following an obscure unsuccessful campaign against Theodore II Lascaris of the Empire of Nicaea, Mitso lost control even over the commoners.
When the nobility proclaimed Constantine Tikh emperor instead, Mitso and his family fled the capital in 1257 and attempted to resist from Preslav and then Mesembria (now Nesebăr). In exchange for asylum and lands, Mitso turned over Mesembria and its environs to Emperor Michael VIII Palaiologos and sought refuge in Nicaea. Here he was given lands in the Troad, where he remained with his family. The date of his death is unknown, but it is likely that he was no longer alive in 1277/1278, when his son Ivan Asen III was put forward as a claimant to the Bulgarian throne by the Byzantine Emperor Michael VIII.
By his marriage with Maria of Bulgaria, Mitso had two known children: