Saddam Hussein's presidency of Iraq included a failed invasion of Kuwait in 1990 that precipitated the Persian Gulf War. Following the war, US officials suspected Iraq of cease-fire violations, including the production of weapons of mass destruction (WMD). In dealing with United Nation arms inspectors, Hussein proved intractable for more than 12 years. On March 20, 2003, a combined military force consisting of 300,000 primarily US and British troops entered Iraq through Kuwait. The reported pretext for the invasion was to locate and destroy chemical, nuclear, and biological WMDs, and depose Hussein. To date, no WMDs have been found. Baghdad fell on April 9. President George W. Bush declared the end of major combat operations on May 1, however, coalition forces remain to stabilize the country, experiencing frequent insurgent attacks. On December 13, Hussein was captured near his home town of Tikrit. Coalition fighters continue to encounter fierce resistance. By May 10, 2007, more than 3382 American and coalition troops had died in Iraq with the civilian casualties estimated at about 62,570.

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In the early 1500's, the Ottomans began their rise to power as the next great Islamic state. The first ruler was Sultan Selim I ("The Grim"). His victory in 1514 at the Battle of Chaldiran over the Safavids of Iran paved the way for Ottoman expansion into northern Iraq, as the Safavids had conquered Iraq in 1509. Son of Selim, Suleyman I ("the Magnificent") succeeded to the throne in 1520, and by 1522 turned his attention to the Safavids, first negotiating a truce with Archduke Ferdinand of Hungary, leaving himself free to wage the first of three major campaigns against Persia. In 1534, he took the cities of Baghdad and most of Iraq from the Persians, an enormous success, leading to almost four centuries of Ottoman rule in Iraq.

Mesopotamia had become known as "Iraq," the center of a large Muslim caliphate. The Abbasid ruling family established a new capital at Baghdad, which prospered. Early in the 13th Century AD, the Mongol leader, Temujin, organized the Mongol tribes into a marauding army over 700,000 strong, and began conquests of China, Persia, and Eastern Europe. He renamed himself Chinggis (Genghis) Khan ("World Conquerer"). A generation later, his grandson, Hulagu, was dispatched to capture the remainder of southwest Asia. In 1258, Hulagu besieged Baghdad, then sacked most of it, slaughtering as many as 800,000 of the inhabitants. He killed the scholars, erecting a pyramid of their skulls, and executed the caliph, al-Musta'sim, the 37th and final Abbisid ruler of a line that had lasted 500 years. Iraq was reduced to tribal culture, never to regain world prominence.

The Persian Sasanians ruled Mesopotamia from 224 AD. They thrived for centuries, but eventually became distracted by fighting the Romans and amongst themselves. Ultimately, an unlikely outside force would topple them. The Arabs had been tribesmen, unorganized and militarily primitive. The new religion of Islam, founded by Muhammad, united the tribes. In 634, the Arab campaign against the Sassanians began. 18,000 Arab tribesmen, led by General Khalid ibn al Walid ("The Sword of Islam") reached the Euphrates delta and began battling the Iranians (Persians), who were rallied by their hero, Rustam. A decisive battle occurred at Al-Qidisiyah, a village south of Baghdad. Though outnumbered six to one, the Arabs defeated the Iranians, exhausted by many battles against the Byzantines. Rustam was killed. The Arabs shortly captured the Sassanid capital at Ctesiphon, ending their dynasty and introducing Islam to the region.

Marcus Licinius Crassus became governor of Syria in 55 BC. A triumvir with Pompey and Julius Caesar, he sought to increase his reputation by invading Parthian Mesopotamia. With seven legions, about 44,000 men, he crossed the Euphrates. However, he strayed from the river into the open desert. Near Carrhae (Harran), the Parthians approached with 10,000 mounted archers. The Romans held a theoretical advantage, but lacked desert warfare experience (fighting at midday in June?), and staggered before the Parthian arrows, fired from compound bows. Also, the Parthian commander, General Suren, had thoughtfully brought 1000 camels to re-supply his archers with arrows. Surrounding the Romans, the Parthians turned the battle into dusty target practice. Only 10,000 Gauls were reported to survive. In attempting to surrender, Crassus was killed. Roman prestige plunged in the east.

In 334 BC, Alexander III ("The Great") crossed the Hellespont (Dardanelles) with 7000 cavalrymen and over 30,000 infantrymen. During this expedition, Alexander defeated the king, Darius III, at the Battle of Issus. Darius retreated to the Plain of Gaugamela, near Arbela (Irbil). There he massed a enormous army and ordered the plain cleared for his scythed chariots and war elephants. Darius' army stood in a massive line. Alexander's outnumbered Macedonian forces attempted to draw the Persians away from the prepared ground. In countering, the Persian cavalry opened gaps in their own line, into which Alexander led his personal cavalry. The Persian chariots charged the Macedonians, which yielded and then decimated their drivers with projectiles. Alexander's elite cavalry turned and attacked from the rear. When Darius saw his troops in disarray, he fled, prompting a full retreat. Alexander had ended the Persian empire founded by Cyrus II.

Assyria developed around the city of Ashur on the upper Tigris, weaker than other states appearing after Hammurabi's dynasty, including the Kassites and the Hurrians/Mitanni. Assyria was long ruled by the Mitanni, but regained autonomy during the Middle Assyrian Empire. In his second year of rule, Shalmaneser I attacked the breakaway state of Uruatru in southern Armenia. Shattuara II of Hanigalbat, leading the rebellion with the aid of the Hittites, blockaded the mountain passes and waterholes. With a desperation born of thirst, the Assyrians pounded the Mitanni kingdom into submission. Afterwards, Shalmaneser claimed to have blinded 14,400 men, a nasty bit of psychological warfare. His inscriptions mention the utter devastation of nine fortified temples, 180 Hurrian cities, and the Hittite and Ahlamu armies. Obviously, the Assyrians were not well-liked.