The Battle of Melitene in 575 (according to other sources 576) marked a major victory of the Eastern Roman Empire against the Persian Sassanid Empire in the long series of wars that the two great powers of the late ancient fought against each other.

In 572 again war broke out between the Romans and the Sassanids.In the years before the battle the Persians under command of their King Chosrau I. succeeded in conquering northern Mesopotamia including the important fortress Dara and the situation looked dire for Eastern Rome, that it is said the Emperor Justin II. became mad due to its direness. Empress Sophia made Tiberios General and Caesar, so in 575 he attempted a counterattack At Melitene on the Euphrat he achieved a much needed victory.

The already venerable Persian king Khosrau I, who himself was present and probably had intended to march to Caesarea in Cappadocia, was found on the road by Eastern Roman troops and then tried to break through to Melitene (direction Euphrates). During the river crossing, the Persian army was however surprised by the Romans, and Khosrau could only with great difficulty escape (see Evagr. HE 5.14). It seems this was the most seriousPersian defeat by the Romans since a long time. Some Roman authors report Chosroes even said after the battle , that the great kings henceforth no longer should ride (or only under certain conditions)themselfes in the war, and indeed his two successors moved unlike previous rulers only exceptionally themselves into battle.

Although the battle was on the Persian side apparently conceived as a shock, it did not lead to the end of the war, but only brought the Sassanid advance to a halt. From then until the war's end 591, there was a stalemate.