Sophronius has been claimed to be of Byzantine Greek, as well as of Syriac descent. A teacher of rhetoric, Sophronius became an ascetic in Egypt about 580 and then entered the monastery of St. Theodosius near Bethlehem. Traveling to monastic centres in Asia Minor, Egypt, and Rome, he accompanied the Byzantine chronicler St. John Moschus, who dedicated to him his celebrated tract on the religious life, Leimõn ho Leimõnon (Greek: “The Spiritual Meadow”) (and whose feast day in the Eastern Orthodox Church, 11 March , is shared with Sophronius'). On the death of Moschus in Rome in 619, Sophronius accompanied the body back to Jerusalem for monastic burial. He traveled to Alexandria, Egypt, and to Constantinople in the year 633 to persuade the respective patriarchs to renounce Monothelitism, a heterodox teaching that espoused a single, divine will in Christ to the exclusion of a human capacity for choice. Sophronius' extensive writings on this question are all lost.
Although unsuccessful in this mission, Sophronius was elected patriarch of Jerusalem in 634. Soon after his enthronement he forwarded his noted synodical letter to Pope Honorius I and to the Eastern patriarchs, explaining the orthodox belief in the two natures, human and divine, of Christ, as opposed to Monothelitism, which he viewed as a subtle form of heretical Monophysitism (which posited a single nature for Christ). Moreover, he composed a Florilegium (“Anthology”) of some 600 texts from the Orthodox Church Fathers in favour of the Orthodox tenet of Dyothelitism (positing both human and divine wills in Christ). This document also is lost.
In his Christmas sermon of 634, Sophronius was more concerned with keeping the clergy in line with the Chalcedonian view of God, giving only the most conventional of warnings of the Saracen advance on Palestine, commenting that the Saracens already controlled Bethlehem. Sophronius, who viewed the Saracen control of Palestine as "unwitting representatives of God's inevitable chastisement of weak and wavering Christians", died soon after the fall of Jerusalem to the caliph Umar I in 637, but not before he had negotiated the recognition of civil and religious liberty for Christians in exchange for tribute - an agreement known as Umari Treaty. The caliph himself came to Jerusalem, and met with the patriarch at the Church of the Holy Sepulchre. Sophronius invited Umar to pray there, but Umar declined, fearing to endanger the Church's status as a Christian temple.
Beside polemics, Sophronius' writings included an encomium on the Alexandrian martyrs Cyrus and John in gratitude for an extraordinary cure of his failing vision. He also wrote 23 Anacreontic (classical metre) poems on such themes as the Muslim siege of Jerusalem and on various liturgical celebrations. His Anacreontica 19 and 20 seem to be an expression of the longing desire he had of the Holy City, possibly when he was absent from Jerusalem during one of his many journeys. The order of the two poems has to be inverted to establish a correct sequence of the diverse subjects. Arranged in this way, the two poems describe a complete circuit throughout the most important sanctuaries of Jerusalem at the end of the 6th century, described as the golden age of Christianity in the Holy Land. Themes of Anacreonticon 20 include the gates of Jerusalem (or Solyma), the Anastasis, the Rock of the Cross, the Constantinian Basilica, Mount Sion, the Praetorium, St. Mary at the Probatica, and Gethsemane. The Mount of Olives, Bethany, and Bethlehem come next in Anacreonticon 19. Sophronius also wrote down the Life of St. Mary of Egypt, which is read on the fifth Thursday of Lent in the Eastern Orthodox Church.
According to the Muslim apocryphal treaty Pact of Umar, caliph Umar ibn al-Khattab came to Jerusalem in 637 after the conquest of Jerusalem and toured the city with Sophronius. During the tour of the Church of the Holy Sepulchre, the time for prayer came, and despite Sophronius's offer to Umar to pray inside the Church, Umar chose to pray outside. According to Islamic tradition, the caliph's reason for declining to pray there was because in the future Muslims might say that Umar prayed here and use it as an excuse to build a mosque there. Therefore, Muslims are not allowed to build a mosque there. So appreciating the caliph's intelligence he gave the keys of the church to him. Unable to refuse it the caliph gave it to a family of Muslims from Medina and asked them to open the church and close it; the keys of the Church of the Holy Sepulchre still remain with the Muslim family.