Khosrow II in the context of "Heraclius"

As part of the early Muslim conquests, which began under Muhammad in 622, the Rashidun Caliphate conquered the Sasanian Empire between 632 and 654. This event led to the decline of Zoroastrianism, which had been the official religion of Persia (or Iran) since the time of the Achaemenid Empire, circa 550 BC. The persecution of Zoroastrians by the early Muslims during and after this conflict prompted many of them to flee eastward to India, where they were taken as refugees by various kings.

While Arabia was witnessing the rise of Islam in the 7th century, Persia was struggling with unprecedented political, economic and social issues as well as military weakness; the Sasanian army had greatly exhausted itself in the Byzantine–Sasanian War of 602–628. Following the execution of Sasanian shah Khosrow II in 628, Persia's internal political stability began to deteriorate rapidly, leading to ten new royal claimants being enthroned within the next four years. Shortly afterwards, Persia was further devastated by the Sasanian Interregnum, a large-scale civil war that began in 628 and resulted in the government's decentralization by 632.

The Byzantine–Sasanian War of 602–628, also called the Last Great War of Antiquity, was fought between the Byzantine Empire and the Sasanian Empire. It was the final and most devastating conflict of the Roman–Persian wars (54 BC – AD 628). The previous war between the two powers had ended in 591 after the emperor Maurice helped the Sasanian king Khosrow II regain his throne. In 602, Maurice was murdered by his political rival Phocas. Khosrow declared 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, the Aegean Sea, and before the walls of Constantinople itself.

From 602 to 622, the Sassanians gradually conquered much of the Levant, parts of Anatolia, and—for the first time—Egypt and several islands in the Aegean Sea. The counter-attacks of the new Byzantine emperor Heraclius from 622 to 626 eventually forced the Persians onto the defensive. Allied with the Avars and Slavs, the Persians attempted to take Constantinople in 626, but were defeated. In 627, allied with Turks, Heraclius invaded the heartland of Persia. After the Battle of Nineveh (627), Iranian forces were finally broken, forcing civil war-torn Persia to seek peace.

The Sasanian civil war of 628–632, also known as the Sasanian Interregnum was a conflict that broke out after the execution of the Sasanian king Khosrow II between the nobles of different factions, notably the Parthian (Pahlav) faction, the Persian (Parsig) faction, the Nimruzi faction, and the faction of general Shahrbaraz. Rapid turnover of rulers and increasing provincial landholder power further diminished the empire. Over a period of four years and fourteen successive kings, the Sasanian Empire weakened considerably, and the power of the central authority passed into the hands of its generals, contributing to its fall.

The Lakhmid kingdom (Arabic: اللخميون al-Lakhmiyyūn), also referred to as al-Manādhirah (المناذرة) or as Banū Lakhm (بنو لخم), was an Arab kingdom that was founded and ruled by the Lakhmid dynasty from c. 268 to 602. Spanning Eastern Arabia and Southern Mesopotamia, it existed as a dependency of the Sasanian Empire, though the Lakhmids held al-Hira as their own capital city and governed from there independently. The kingdom was a participant in the Roman–Persian Wars, in which it fought as a Persian ally against the Ghassanid kingdom, which was ruled by a rival Arab tribe and existed as a dependency of the Roman Empire. While the term "Lakhmids" has been applied to this kingdom's ruling dynasty, more recent scholarship prefers to refer to them as the Naṣrids.

The Nasrid dynasty's authority extended over to their Arab allies in Al-Bahrain (eastern cost of Arabia) and Al-Yamama. In 602, the Persian king Khosrow II deposed and executed the last Nasrid ruler Al-Nu'man III and annexed the Lakhmid kingdom, triggering a revolt by his Arab allies in Najd. The ensuing disorder between anti-Persian rebels and pro-Persian loyalists in the kingdom culminated in the Battle of Dhi Qar, which resulted in a defeat for the Persian army and their loyalists, thereby ending the Persian hegemony over Eastern Arabia. The success of the rebellion and the victory against the Persians at Dhi Qar roused political confidence, enthusiasm, and self-consciousness among the Arabs. Coupled with increasing instability in Persia proper after the downfall of Khosrow in 628, these events heralded the decisive Battle of Qadisiyya in 636 and the Muslim conquest of Persia.