Born into a wealthy family and received a rhetorical education from the world-renowned Libanius, under whom Basil, Gregory of Nazianzus, and John Chrysostom all studied. After his time there, along with John, he studied under Diodore of Tarsus in Tarsus. Under the persuasive influence of John, he recommitted himself to an ascetic church life, pushing away his urges to become a lawyer and marry. He stayed with Diodore from 370 to 386, being ordained a priest in 383. In 392 he was appointed a bishop of nearby Mopsuestia, where he remained until his death in 428.

Best known for his exegesis, T. produced commentaries on the entire Pentateuch, Psalms, the major and minor prophets, Job, Ecclesiastes, Song of Songs, Matthew, Luke, John, Acts, Hebrews, and all of the Pauline letters. We do not have all of these today, however. He perpetuates the work of Diodore, focusing on the literal meaning of a text through what may be called "literary interpretation." T.'s chief dogmatic work, De incarnatione, is lost but for a few fragments. There are polemics against Arianism and Macedonianism in fragments as well. He also composed some ascetic works, which also are mostly non-extant. Finally, he produced the catechetical homilies, which were discovered in the early^20th century. These explain the creed, the Lord's Prayer, baptism, and the Eucharist, and provide a gold mine of historical data concerning liturgy.

T. was considered the leading theologian of the Persian church along with Nestorius. He, however, had the misfortune of being condemned as a forerunner of Nestorianism at the Second Council of Constantinople (553) well after his death. The Council had access to only a portion of his work, which did not provide an accurate picture of his theology anyway. On this basis, however, many of his works were destroyed, and most of what is still extant has been preserved in Syriac translation. The Syrian church continued to hold him in high esteem, despite the Council's ruling. He was an advocate of symmetrical Christology in which the divine and human natures of Christ are in perfect correspondence. "The assumed man corresponds to the assuming Logos, while the moral progress of the Son of man corresponds to the gracing action of the Son of God, the two being connected by a perfect synergy. The unifying factor is...the prosopon of the redeemer." (Bruns, DECL 563) He argued for the divinity of the Spirit in his works against the Macdonians, applying the homoousios of the Father and Son in Nicaea to the Holy Spirit as well. He also was a rigorous defender of Nicene orthodoxy against the Arians and defended orthodox Christology against Apollinarism.