The Byzantine–Sasanian War of 602–628 was the final and most devastating of the series of wars fought between the Byzantine Empire and the Sasanian Empire of Iran. The previous war between the two powers had ended in 591 after Emperor Maurice helped the Sasanian king Khosrow II regain his throne. In 602 Maurice was murdered by his political rival Phocas. Khosrow proceeded to declare war, ostensibly to avenge the death of the deposed emperor Maurice. This became a decades-long conflict, the longest war in the series, and was fought throughout the Middle East: in Egypt, the Levant, Mesopotamia, the Caucasus, Anatolia, Armenia, the Aegean Sea and before the walls of Constantinople itself.

While the Persians proved largely successful during the first stage of the war from 602 to 622, conquering much of the Levant, Egypt, several islands in the Aegean Sea and parts of Anatolia, the ascendancy of the emperor Heraclius in 610 led, despite initial setbacks, to a status quo ante bellum. Heraclius' campaigns in Iranian lands from 622 to 626 forced the Persians onto the defensive, allowing his forces to regain momentum. Allied with the Avars and Slavs, the Persians made a final attempt to take Constantinople in 626, but were defeated there. In 627, allied with Turks, Heraclius invaded the heartland of Persia. A civil war broke out in Persia, during which the Persians killed their king, and sued for peace.

By the end of the conflict, both sides had exhausted their human and material resources and achieved very little. Consequently, they were vulnerable to the sudden emergence of the Islamic Rashidun Caliphate, whose forces invaded both empires only a few years after the war. The Muslim armies swiftly conquered the entire Sasanian Empire as well as the Byzantine territories in the Levant, the Caucasus, Egypt, and North Africa. In the following centuries, the Byzantine and Arab forces would fight a series of wars for control of the Near East.