At the beginning of his reign Shahanshah Khosrau I Anushirvan (Immortal Soul) concluded an "Eternal Peace" with the Roman Emperor Flavius Petrus Sabbatius Justinian I (527–565) in 532, who wanted to have his hands free for the conquest of Africa and Sicily. But (according to Procopius) his successes against the Vandals and Goths caused Khosrau I to begin the war again in 540.
He invaded Syria and sacked the great city of Antioch, deporting its people to Mesopotamia, where he built for them a new city near Ctesiphon under the name of "Khosrau-Antioch" or "Chosro-Antioch". During the following years he secured the defection of Lazica and fought inconclusively in Mesopotamia.
In 545, an armistice was concluded, but in 547 the Lazi returned to their Roman allegiance and the Lazic War resumed, continuing until a truce was agreed in 557. At last, in 562, a peace was concluded for fifty years, in which the Persians left Lazica to the Romans, and promised not to persecute the Christians, if they did not attempt to make proselytes among the Zarathustrians; on the other hand, the Romans had to pay annual subsidies to Persia.
Meanwhile in the east, the Hephthalites had been attacked by the Turks (Göktürks). About 560, Khosrau I united with them to destroy the Hephthalite Empire. In 567 he conquered Bactria, while he left the country north of the Oxus to the Turks. Many other rebellious tribes were subjected. About 570 the Himyarite dynasts of Yemen, who had been subdued by the Ethiopians of Axum, applied to Khosrau I for help. The Emperor Khosrau sent a fleet with a small army under Vahriz, who expelled the Ethiopians. From that time till the conquests by Islam, Yemen was dependent on Persia, and a Persian governor resided here. In 572, Armenia and Iberia rebelled against Persia with Roman support, beginning a new war in which Khosrau I conquered the city of Dara on the Euphrates in 573, but after a largely unsuccessful incursion of Anatolia in 576 he was heavily defeated by the Romans in a battle near Melitene. He sued for peace in 579, but while negotiations with the Emperor Tiberius II (578–582) were still going on, Khosrau I died and was succeeded by his son Hormizd IV (579–590).