John's family were Christians of Damascus who served the administration, first Byzantine and then Umayyad, and he appears to have held a financial post under the caliph before withdrawing to the monastery of Mar Saba in the Judaean desert. That biography is the key to his position. When the emperors in Constantinople began suppressing the veneration of images in the 720s, the most effective theological opposition came from a monk living outside their jurisdiction, in a territory the emperor could not reach.
His major work, the Fount of Knowledge, is in three parts: a philosophical vocabulary, a catalogue of heresies, and the Exact Exposition of the Orthodox Faith, which sets out the whole of Christian doctrine in order. It is the first systematic summa in the Greek tradition, it was translated into Latin in the twelfth century and used by the western scholastics, and it remains a standard reference in Orthodox theology. He was explicit that he was not being original: he described himself as gathering what the fathers had said, and that self-effacement is part of why the book was trusted.
The catalogue of heresies contains what is generally taken to be the earliest Christian discussion of Islam, written by a man who had grown up under Muslim rule and knew the Quran at first hand. He treats it as a Christian heresy rather than a separate religion, which is how the Greek world classified it for centuries afterwards.