518 – 553 (council, 5 May – 2 June 553); acceptance in the West completed by the late 6th c.

The Three Chapters controversy and the Fifth Ecumenical Council (Second Constantinople, 553)

Justinian I sought to reconcile the Monophysites, not least under the influence of his Monophysite wife Theodora. Around 544, on the advice of Theodore Askidas, he issued an edict condemning "three chapters." These were the person and writings of Theodore of Mopsuestia, the anti-Cyrilline writings of Theodoret of Cyrus, and the letter of Ibas of Edessa to Maris the Persian.

The edict provoked strong resistance in the West. An African council excommunicated Pope Vigilius for his wavering. Facundus of Hermiane wrote an extensive treatise, "In Defense of the Three Chapters," and Illyrian bishops protested in a letter to the emperor. In May 550 a special local council met at Mopsuestia. On the basis of the diptychs and the testimony of elders, it confirmed that Theodore's name had long been struck from commemoration.

Pope Vigilius was summoned to Constantinople in 547. Under pressure from Justinian, after much wavering and mutual excommunications with Patriarch Menas, he agreed to condemn the three chapters.

The Fifth Ecumenical Council was convened in 553 under the presidency of Patriarch Eutychius of Constantinople. Western participation was minimal – only a few African bishops. The council confirmed the condemnation of the three chapters. It interpreted Chalcedon in the spirit of the later Cyril of Alexandria ("one of the Trinity was crucified in the flesh"). It also anathematized Origen, Evagrius Ponticus, and Didymus the Blind for their teaching on the pre-existence of souls and universal restoration.

Despite these concessions, the Monophysites were never reconciled with the Church. Acceptance of the council in the Latin West took half a century. It was completed only under Popes Pelagius I and Gregory the Great.