The Byzantine–Sassanid War of 602–628 is the final and most devastating of the series of wars fought between the Byzantine (Eastern Roman) Empire and the Sassanid Empire of Iran.

The previous war between the two powers had ended in 591 after Emperor Maurice had helped the Sassanian king Khosrau II regain his throne.

In 602, Maurice was murdered by his political rival Phocas.

Khosrau proceeded to declare war, ostensibly to avenge Maurice's death.

This beomes a decades-long conflict, the longest war in the series, and is fought throughout the Middle East and eastern Europe: in Egypt, the Levant, Mesopotamia, the Caucasus, Anatolia, and even before the walls of Constantinople itself.While the Persians prove largely successful during the first stage of the war from 602 to 622, conquering much of the Levant, Egypt, and parts of Anatolia, the ascendancy of emperor Heraclius in 610 led, despite initial setbacks, to the Persians' defeat.

Heraclius' campaigns in Persian lands from 622 to 626 force the Persians onto the defensive and allow his forces to regain momentum.

Allied with the Avars, the Persians make a final attempt to take Constantinople in 626, but are defeated there.

In 627, Heraclius invades the Persians' heartland and forces them to sue for peace.By the end of the conflict both sides have exhausted their human and material resources.

Consequently, they are vulnerable to the sudden emergence of the Islamic Rashidun Caliphate, whose forces invade both empires only a few years after the war.

The Muslim forces swiftly conquer the entire Sassanid Empire, and deprive the Byzantine Empire of its territories in the Levant, the Caucasus, Egypt, and North Africa.

Over the following centuries, half the Byzantine Empire and the entire Sassanid Empire will come under Muslim rule.