From the 8 October to 1 November 451, the Ecumenical Council of Chalcedon met to define the doctrine of the two natures of Jesus Christ as fully human and fully divine.

Those who did not accept the doctrine of the two natures [physis] of Christ would be called monophysites by the Chalcedonian Christians, though those who believe Christ had only one nature prefer to be called miaphysites. For both miaphysite and Chalcedonian Christians, Christ must be fully divine and fully human if he is to be the savior of humanity by reuniting God and Man after the fall of Adam. However, where the Chalcedonians express the union without confusion of divinity and humanity in Christ by using the terminology of two natures, the miaphysite Christians refer to two aspects of one nature. Unfortunately, historical misunderstandings and differences in theological language led to a split between the miaphysites who are represented today by the Oriental Orthodox Churches and the Chalcedonians who are represented by the Catholic and Orthodox Churches.

The Council also passed a series of canons, including the 28th canon which sought to raise the status of the Patriarchy of Constantinople to the level of that in Rome. This 28th Canon would not be confirmed by Pope Leo in Rome.