When Patriarch Flavian II of Antioch was deposed in 512 St. Severus was elected Patriarch of Antioch, being enthroned on 6 November 512. Following the rise to power of Emperor [[Justinian I]] the Saint was summoned to Constantinople, where the emperor attempted to persuade him to accept Chalcedon. When St. Severus refused the emperor ordered him to be killed, but he was saved by St. Theodora, the emperor's wife, who was the daughter of a priest from Syria and an opponent of Chalcedon. At her urging St. Severus fled the capital, after which Emperor Justinian declared him deposed and in 518 placed a supporter of Chalcedon on the patriarchal throne of Antioch.
St. Severus fled Constantinople for Egypt, where he met with Pope Timothy II and took refuge in a number of different monasteries disguised as a simple monk. Throughout his travels in Egypt St. Severus preached the Orthodox Faith and strengthened the faithful in their resistance to Chalcedon and Eutychianism. He also wrote many books and letters against heresies. Although he wrote in Greek his writings have been primarily preserved in Syriac.
In 535 St. Severus returned to Constantinople to discuss the reunification of the Church with Emperor Justinian. During his stay in the city he brought Patriarch Anthimus of Constantinople to reject Chalcedon, but the schism as a whole was unable to be healed at that time and in 536 the emperor had St. Severus formally excommunicated by the hierarchs who favored Chalcedon on false charges.
Upon returning to Egypt, St. Severus settled in the home of a layman, Dorotheus, in the city of Sakha and continued to teach and work many miracles. On 8 February 538 he fell asleep in the Lord. His relics were then translated to the Monastery of el-Zugag to the west of Alexandria, working many signs and wonders in the process.