His namesake maternal grandfather was the third son of John II Komnenos and Piroska of Hungary. He was the senior surviving son of John II at his death but his younger brother Manuel I Komnenos successfully claimed the throne for himself.
Emperor Manuel made Isaac governor of Isauria and the town of Tarsus in present-day eastern Turkey, where he started a war with the Armenian Kingdom of Cilicia and was subsequently captured by the enemy. As Emperor Manuel had died in the meantime (1180), nobody seems to have greatly cared about Isaac's fate, and he remained a prisoner for a long time, which seems to have done nothing for improving his disposition in general. As he was married to an Armenian princess when on Cyprus, his terms of captivity may not have been too harsh.
Finally his aunt Theodora Komnene, who had an affair with the new Emperor Andronikos I Komnenos (1183–1185) convinced the Emperor to contribute to his ransom, as did his stepfather Constantine Makrodoukas and Andronikos Doukas, another relative and a childhood friend, a sodomite and debaucher, as Niketas tells us. Strangely enough, the Templars (the Phreri, as Niketas Choniates calls them) contributed as well.
When Isaac was released in 1185, it was clear he had tired of the Imperial service. He used the rest of the money to hire a troop of mercenaries and sailed to Cyprus. He presented falsified imperial letters that ordered the local administration to obey him in everything and established himself as ruler of the island.
Constantine Makrodoukas and Andronikos Doukas had had to stand surety for Isaac's fealty to the Emperor. When he failed to return, Andronikos I Komnenos had them arrested for treason, although Constantine had been his loyal supporter so far. Andronikos I was afraid that Isaac would try to usurp the throne, as a water-oracle conducted by the courtier Stephen Hagiochristophorites had given I (iota) as the initial of the next Emperor. When the prisoners were led out of prison to face the charges, Hagiochristophorites started to stone them and forced the others to join him. Both prisoners were then impaled at the front of the Mangana palace.
Another oracle gave the date when the next Emperor would start to rule, and Andronikos I was greatly relieved, as the time was much too short for Isaac to make the crossing from Cyprus.
Meanwhile Isaac had taken many other Romans into his service. He created an independent patriarch of Cyprus, who crowned him as emperor in 1185. According to Niketas Choniates, he soon started to plunder Cyprus, raping women and defiling virgins, imposing overly cruel punishments for crimes and stealing the possessions of the citizens. "Cypriots of high esteem, comparable to Job in riches now were seen begging in the streets, naked and hungry, if they were not put to the sword by this irascible tyrant." Furthermore, he had the foot of his old teacher Basil Pentakenos hacked off, which Niketas finds even more despicable.
In 1185 Isaac II Angelos became Emperor after a popular uprising at Constantinople. He raised a fleet of 70 ships to take back Cyprus. The fleet was under the command of John Kontostephanos and Alexios Komnenos, a nephew once removed of the Emperor. Neither seems to have been very fit, as John was quite old, and Alexios had been blinded by order of Andronikos I.
They landed in Cyprus, but Margaritone of Brindisi, a pirate in the service of King William II of Sicily (1166–1189) captured the ships after the troops had left them. Isaac, or more likely Margaritone, won a victory over the Byzantine troops and captured the captains, whom he took off to Sicily, while the rest of the sailors remained on Cyprus, to fend for themselves as best they could. "Only much later did they return home, if they had not perished altogether."
In 1192 the fiancée and the sister of the English King Richard I Lionheart were shipwrecked on Cyprus and were taken captive by Isaac. In retaliation Richard (whom Niketas calls "King of the Inglines") conquered the island while on his way to Tyre. Isaac was taken prisoner near Cape St. Andreas on the Karpass Peninsula, the northernmost tip of the island. According to tradition, Richard had promised Isaac not to put him into irons, so he kept him prisoner in chains of silver. Isaac was turned over to the Knights of St. John, who kept him imprisoned in Margat near Tripoli until he was released in c. 1194.
Isaac now traveled to the Sultanate of Rum, where he attempted to gain support against the new Byzantine Emperor Alexios III Angelos (1195–1203). However, Isaac's ambitions came to nothing, as he died by poisoning in 1195 or 1196.
Isaac is described as an irascible and violent man, "boiling with anger like a kettle on the fire", but Niketas clearly is not very partial to him. The cruelties attributed to him pale somewhat in comparison with Emperor Andronikos I. He seems to have been in league with William II of Sicily, who was a powerful thorn in the side of the Empire, which helped him to hold the island as long as he did, and had close connections to sultan Saladin as well.
Later she lived in Provence, where in 1199 she encountered Count Raymond VI of Toulouse and, once again, Joan Plantagenet, who was now Raymond's wife and pregnant with his second child. The couple split up suddenly and Raymond began a relationship (a marriage, some say) with Isaac's daughter. This was over by about 1202, when she married Thierry, an illegitimate son of Baldwin, Count of Flanders. These two sailed from Marseille in 1204, with a convoy of warriors who intended to join the Fourth Crusade and did not turn aside to Constantinople. On reaching Cyprus, the couple attempted to claim the island as inheritors of Isaac. The attempt failed, and they fled to Armenia.