Around 370, he was living in a monastic community in Aquileia when he met Jerome. In about 372, Rufinus travelled to the eastern Mediterranean, where he studied in Alexandria under Didymus the Blind for some time. From there he moved to Jerusalem, where he founded a monastery.
He first settled in Egypt, hearing the lectures of Didymus, the Origenistic head of the catechetical school at Alexandria, and also cultivating friendly relations with Macanus the elder and other ascetics in the desert. In Egypt, if not even before leaving Italy, he had become intimately acquainted with Melania the Elder, a wealthy and devout Roman widow; and when she removed to Palestine, taking with her a number of clergy and monks on whom the persecutions of the Arian Valens had borne heavily, Rufinus (about 378) followed her.
While his patroness lived in a convent of her own in Jerusalem, Rufinus, at her expense, gathered together a number of monks in a monastery on the Mount of Olives, devoting himself at the same time to the study of Greek theology. This combination. of the contemplative life and the life of learning had already developed in the Egyptian monasteries. When Jerome came to Bethlehem in 386, the friendship formed at Aquileia was renewed. Another of the intimates of Rufinus was John, bishop of Jerusalem, and formerly a Nitrian monk, by whom he was ordained to the priesthood in 390.
In 394, in consequence of the attack upon the doctrines of Origen made by Epiphanius of Salamis during a visit to Jerusalem, a fierce quarrel broke out, which found Rufinus and Jerome on different sides; and, though three years afterwards a formal reconciliation was brought about between Jerome and John, the breach between Jerome and Rufinus remained unhealed.
In the autumn of 397 Rufinus embarked for Rome, where, finding that the theological controversies of the East were exciting much interest and curiosity, he published a Latin translation of the Apology of Pamphilus for Origen, and also (398-99) a somewhat free rendering of the Περι Αρχων (or De Principiis) of that author himself. In the preface to the latter work he referred to Jerome as an admirer of Origen, and as having already translated some of his works with modifications of ambiguous doctrinal expressions. This allusion annoyed Jerome, who was exceedingly sensitive as to his reputation for orthodoxy, and the consequence was a bitter pamphlet war, very wonderful to the modern onlooker, who finds it difficult to see anything discreditable in the accusation against a biblical scholar that he had once thought well of Origen, or in the countercharge against a translator that he had avowedly exercised editorial functions as well.
At the instigation of Theophilus of Alexandria, Pope Anastasius I summoned Rufinus from Aquileia to Rome to vindicate his orthodoxy; but he excused himself from a personal attendance in a written Apologia pro fide sua. The pope in his reply expressly condemned Origen, but left the question of Rufinus's orthodoxy to his own conscience. He was, however, regarded with suspicion in orthodox circles (cf. the Decretum Gelasii, 20) in spite of his services to Christian literature.
In 408 we find Rufinus at the monastery of Pinetum (in the Campagna?); thence he was driven by the arrival of Alaric to Sicily, being accompanied by Melania in his flight. In Sicily he was engaged in translating the Homilies of Origen when he died in 410.
Many of his extant works are defenses of himself against attacks by Jerome.
Origen's commentary on the New Testament Epistle to the Romans survives only in an abbreviated version by Rufinus; his De principiis (On first principals) also survives only in Rufinus's translation. Jerome, earlier a friend of Rufinus, fell out with him and wrote at least three works opposing his opinions and condemning his translations as flawed. For instance, Jerome prepared a (now lost) translation of Origen's De principiis to replace Rufinus's translation, which Jerome said was too free.
The other translations of Rufinus are