Constantine was opposed by his father's chamberlain Artabasdus, who attacked his army while they were on campaign against the Arabs in Anatolia. Artabasdus declared that Constantine had been killed in battle and seized power in Constantinople. Constantine, however, fled to Isauria, rallied his supporters, and besieged the capital in 742. By the end of 743 he had retaken the city and had Artabasdus blinded.
After this he reorganized the themes, the military districts of the empire, and created new divisions called tagmata. He organized these so that they would be more difficult to use in conspiracies. With this reorganized army he recaptured land from the Arabs in 751, who were involved in a civil war of their own. He also defeated the Bulgars at Anchialus in 763.
Constantine continued the iconoclasm of his father Leo III, actively persecuting iconophiles and monasteries. In 753 he called a council of iconoclast bishops and clergy, one of the smallest councils ever, to proclaim the veneration of icons a heresy. This was very unpopular among the general population. In 766 he persecuted iconophile monks and nuns by forcing them to hold hands together in the Hippodrome, and had a mob lynch an iconophile hermit named Stephen. He also proclaimed that relics and prayers to the saints were heretical.
Constantine died on September 14, 775 while on campaign against the Bulgars. Iconophiles considered his death a divine punishment. They spread the rumour that he had defecated in his baptismal font as a baby, and began to use the "Copronymus" nickname. In the 9th century he was disinterred and his remains thrown into the sea.