The Sassanids of Persia under Ardashir I destroyed the Parthian Empire and conquered the region in 224 AD.
During the 240s and 250’s AD, the Sassanids gradually conquered the independent states, culminating with Assur in 256 AD. The region was thus a province of the Sassanid Empire for over four centuries, and became the frontier and battle ground between the Sassanid Empire and Byzantine Empire, with both empires weakening each other, paving the way for the Arab-Muslim conquest of Persia in the mid-7th century.
The Arab Islamic conquest in the mid-7th century AD established Islam in Iraq and saw a large influx of Arabs. Under the Rashidun Caliphate, the prophet Muhammad’s cousin and son-in-law, Ali, moved his capital to Kufa when he became the fourth caliph. The Umayyad Caliphate ruled the province of Iraq from Damascus in the 7th century.
The Abbasid Caliphate built the city of Baghdad along the Tigris in the 8th century as its capital, and the city became the leading metropolis of the Arab and Muslim world for five centuries. Baghdad was the largest multicultural city of the Middle Ages, peaking at a population of more than a million, and was the center of learning during the Islamic Golden Age. The Mongols destroyed the city and burned its library during the siege of Baghdad in the 13th century.
In 1257, Hulagu Khan amassed an unusually large army, a significant portion of the Mongol Empire’s forces, for the purpose of conquering Baghdad. When they arrived at the Islamic capital, Hulagu Khan demanded its surrender, but the last Abbasid Caliph Al-Musta’sim refused. This angered Hulagu, and, consistent with Mongol strategy of discouraging resistance, he besieged Baghdad, sacked the city and massacred many of the inhabitants. Estimates of the number of dead range from 200,000 to a million.
The Mongols destroyed the Abbasid Caliphate and Baghdad’s House of Wisdom, which contained countless precious and historical documents. The city has never regained its previous pre-eminence as a major center of culture and influence. Some historians believe that the Mongol invasion destroyed much of the irrigation infrastructure that had sustained Mesopotamia for millennia. Other historians point to soil salination as the culprit in the decline in agriculture.
The mid-14th-century Black Death ravaged much of the Islamic world. The best estimate for the Middle East is a death rate of roughly one-third.
In 1401, a warlord of Mongol descent, Tamerlane (Timur Lenk), invaded Iraq. After the capture of Baghdad, 20,000 of its citizens were massacred. Timur ordered that every soldier should return with at least two severed human heads to show him. Timur also conducted massacres of the indigenous Assyrian Christian population, hitherto still the majority population in northern Mesopotamia, and it was during this time that the ancient Assyrian city of Assur was finally abandoned.
During the late 14th and early 15th centuries, the Black Sheep Turkmen ruled the area now known as Iraq. In 1466, the White Sheep Turkmen defeated the Black Sheep and took control. From the earliest 16th century, in 1508, as with all territories of the former White Sheep Turkmen, Iraq fell into the hands of the Iranian Safavids. Owing to the century long Turco-Iranian rivalry between the Safavids and the neighboring Ottoman Turks, Iraq would be contested between the two for more than a hundred years during the frequent Ottoman-Persian Wars.