His works were so popular that of any author from late antiquity, only the writings of Augustine of Hippo and John Chrysostom survive in a greater number of manuscripts than Jacob's.

[6] His work earned him many nicknames, including "Flute of the Holy Spirit" (which also belonged to his predecessor Ephrem the Syrian), and "Lyre of the Believing Church" (in Antiochene Syriac Christianity).

Jacob was born around the middle of the fifth century in the village of Kurtam (ܟܘܪܬܘܡ) on the Euphrates in the ancient region of Serugh, which stood as the eastern part of the province of Commagene (corresponding to the modern districts of Suruç and Birecik).

He was educated in the famous School of Edessa and became chorepiscopus back in the Serugh area, serving rural churches of Haura (ܚܘܪܐ, Ḥaurâ).

His tenure of this office extended over a time of great trouble to the Christian population of Mesopotamia, due to the fierce war carried on by the Sasanian emperor Kavadh I within the Roman borders.

[8] In 519 and at the age of 67, Jacob was elected bishop of the main city of the area, called in Syriac Baṭnān d-Sruḡ (ܒܛܢܢ ܕܣܪܘܓ).

As Jacob was born in the same year as the controversial Council of Chalcedon, he lived through the intense rifts that split Eastern Christianity, which led to most Syriac speakers being separated from Byzantine communion.

Even though imperial persecution of anti-Chalcedonians became increasingly brutal towards the end of Jacob's life, he remained surprisingly quiet on such divisive theological and political issues.

Paul Bedjan's edition of selected metrical homilies (Paris 1905–1908) containing 146 pieces all written throughout in dodecasyllabic metre, and those published deal mainly with biblical themes, though there are also poems on such subjects as the deaths of Christian martyrs, the fall of the idols and the First Council of Nicaea.

[11] Of Jacob's prose works, which are not nearly so numerous, the most interesting are his letters, which throw light upon some of the events of his time and reveal his attachment to Miaphysitism, which was then struggling for supremacy in the Syriac churches, and particularly at Edessa, over the opposite teaching of Nestorius.

[12][13] Towards the end of his life, the fate of Miaphysite leaders such as himself took a turn for the worse with the accession of Justin I (r. 518–527) to the throne of the Byzantine Empire.

First, on March 28, 519, Justin adopted a pro-Chalcedonian text known as the Formula of Faith which had been written by Pope Hormisdas a few years beforehand, in 515.

[21] Manuscripts of Jacob's homilies are also found in multiple languages beyond Syriac to which they were translated, including Coptic,[22] Georgian, Armenian, Arabic,[23][24] and Ethiopic.