He was born in Trebizond, lived and taught in Italy and eventually died in Constantinople. He is considered as a controversial figure of the late Byzantine era. He was praised and respected for his outstanding knowledge not only of theology and philosophy, but also of the natural sciences, medicine, rhetoric and poetry, all of which earned him the epithet the Philosopher (o Φιλόσοφος).
Amiroutzes was first attested as a lay advisor to the imperial delegation to the Council of Ferrara-Florence. There he strongly supported the union of churches but upon return to Constantinople he made statements against the papal primacy and Filioque. According to a papal document 100 florins were given to protonotarios George as a subsidy; it was conjectured that Amiroutzes was thus bribed to support the union.
However, he was denounced by his fellow Greeks as an opportunist, a traitor and a renegade for his familiarity with Sultan Mehmed the Conqueror. He was a nephew to the Grand Vizier Mahmud Pasha of the Ottoman Empire, and helped speed the fall of the Empire of Trebizond by persuading Emperor David to surrender to the Ottomans to prevent bloodshed to its inhabitants. Sultan Mehmed sent the Emperor, his family and nobles (including Amiroutzes himself) on one of his ships and sent them to Constantinople. The rest of the inhabitants of Trebizond he divided into three classes: the first became the servants and slaves of Mehmed and his followers; the second were transported to Constantinople to settle there; and the third part were exiled from the city.
Some years later, his former monarch David was executed. The traditional story states that David had received a letter from his niece Theodora, the wife of Uzun Hassan of the Ak Koyunlu, asking that one of his sons or his nephew Alexios be sent to her; this letter fell into Amiroutze' hands, who, to prove his loyalty to the Sultan, passed it on to Mehmed. The Sultan claimed this was evidence of treason, and executed the inconvenient former monarch and his sons.
After Athens fell to the Ottoman forces, Amiroutzes fell in love with one of the prisoners from that conquest, the widow of the last Duke of Athens. He desired to marry her, despite the fact his own wife and children were still alive. When the patriarch Joasaph Kokkas refused to consent to this marriage, Amiroutzis, helped by his cousin Mahmud Pasha, dethroned the patriarch and compelled him to shave his beard as punishment, and Amiroutzes also punished the high ecclesiastical official, whom he unsuccessfully tried to bribe to assist him convince the patriarch, by having the man's nose slit. Amiroutzes met his end while playing at dice, the dice-box in his hand.
George Amiroutzes himself was very popular with the Ottoman court, and one of the advisors of Mehmed the Conqueror on Christianity and Greco-Roman philosophy. He was granted land by the Ottoman Sultan and one of his sons, named after Mehmed the Conqueror, was charged with responsibility for the Greek scriptoria in the Empire. 
- Dialogus de fide
- Letter to Bessarion on the Fall of Trebizond
- Letters to Theodore Agallianos about Agallianos's book On Providence
- A letter on the Council at Florence, authenticity disputed
- various poems dedicated to Mehmed II and others
- Bart Janssens, Jacques Noret, Bram Roosen, Peter van Deun, Studies in Greek Patristic and Byzantine Texts Presented to Jacques Noret for his Sixty-Fifth Birthday, 2004, Peeters Publishers, ISBN 90-429-1459-9
- Bart Janssens, Peter van Deun, George Amiroutzes and his poetical oeuvre
- Карпов, С. П. (Karpov S. P.) (1981). Трапезундская империя и западноевропейские государства в XIII-XV вв. (The Empire of Trebizond and Western European States in the 13th-15th Centuries). Moscow: Moscow University publishing house. p. 141.
- William Miller, Trebizond: The Last Greek Empire of the Byzantine Era (Chicago: Argonaut, 1926), pp. 105f
- Miller, Trebizond, pp. 108f
- Miller, Trebizond, p. 112
- Anthony Bryer, "The Pontic Greeks before the Diaspora", Journal of Refugee Studies, (1991) 4, 315-334