Cyril of Alexandria, defending the unity of Christ against Nestorius earlier in the fifth century, taught that after the incarnation the Word of God had one nature, mia physis, made flesh, a phrase he believed he had inherited from earlier fathers though it seems to have originated as a mistaken attribution. When the Council of Chalcedon met in 451, it defined Christ instead as one person known in two natures, divine and human, united without confusion, change, division or separation, a formula meant to protect both Christ's full divinity and full humanity against different errors on either side.
The bishops of Egypt, Syria and Armenia present at or reacting to Chalcedon read the two-natures language as a betrayal of Cyril's formula and, by extension, as tipping back toward the very error, dividing Christ into two separate subjects, that Cyril had spent his career opposing. Alexandria's own patriarch, Dioscorus, was deposed at the council, and the churches that followed his Christology refused to accept Chalcedon's definition, a rupture that has lasted, largely unhealed institutionally, for more than fifteen centuries.
Each of the resulting Oriental Orthodox churches, Coptic, Syriac, Armenian, Ethiopian, Eritrean and Malankara, developed its own liturgy, calendar and patriarchate independently, but all trace their distinct existence to this single fifth-century Christological disagreement rather than to any difference in geography or governance alone.