Rufinus served as consul in 392 before becoming Praetorian Prefect at Constantinople. During the period immediately after Theodosius' death in January 395 Rufinus was virtually the ruler of the Eastern Roman empire, since he exercised great influence over the young and weak-willed Emperor Arcadius. He attempted to further join himself to Arcadius by marrying his daughter to the young emperor, however this plan was stymied by another of the imperial ministers, Eutropius. Outwardly loyal, he was a traitor. In early 395 he had a secret meeting with Alaric outside Constantinople. Shortly afterward, Alaric and his Visigoths ravaged Thrace, but spared the holdings of Rufinus. Probably under orders, the military in the area did not oppose Alaric, who then moved his forces west (395). Rufinus' negative influence over the Eastern Empire came to a violent end on 27 November 395 when he was assassinated by Gothic mercenaries under Gainas. Rufinus had hated the western magister militum Stilicho, and his influence over Arcadius prevented Stilicho from crushing Alaric when the Roman general had the chance. Stilicho had trapped Alaric and the Visigoths in Greece (395), but was commanded by Arcadius (Rufinus) to vacate eastern territory. Stilicho loyally obeyed the order and returned his forces west across the border.
Rufinus had a sister, Silvania, who wrote a pair of hymns and a short account of a journey to the East which were discovered at Arezzo in 1895.