[2][3] At the beginning of his reign, as he was underage, he stood under the regency of Anna Palaiologina Kantakouzene.
Constantine continued his father's war against Nikephoros I Komnenos Doukas of Epirus and his Angevin allies.
The campaign of 1295 resulted in Thessalian occupation of the fortresses that Nikephoros had designated as the dowry of his daughter Thamar Angelina Komnene when she married Philip I of Taranto, son of King Charles II of Naples and Maria of Hungary.
His wife is unknown; Karl Hopf reported that she was called Anna Evagionissa, and that she outlived Constantine, dying in 1317.
[3] The couple had at least one child, John II Doukas, who succeeded as ruler of Thessaly.