Leaving Egypt in 331 BC, Alexander III the Great (32; r.336-323 BC) marched eastwards into Mesopotamia and defeated Darius III (c.50; r.336-330 BC) on 1 October at the Battle of Gaugamela. Darius fled to Ecbatana (=Hamadan), but Alexander marched to Babylon where the Persian governor Mazaeus (c.385-328 BC) surrendered the city without a fight.
Seleucus-I (c.77; r.305-281 BC)
When Alexander died 10/11 June 323 BC, Perdiccus (d.321 or 320 BC) became regent of Alexander’s Empire and the territories were divided between Alexander’s generals. At the Partition of Babylon (323 BC) Arcesilaus was given the satrapy of Mesopotamia; Seleucus was put in charge of the cavalry. War soon broke out between the generals and when Perdiccus was assassinated another meeting was called. At the Partition of Triparadisus (321 BC), Babylonia was assigned to Seleucus.
In 315 BC Antigonus-I (c.81; r.306-301 BC) entered Babylon and Seleucus had to flee. He took refuge with Ptolemy-I in Egypt and they became allies. Antigonus appointed Peithon son of Agenor as the satrap of Babylon. Ptolemy’s defeat of Antigonus’ son Demetrius-I Poliorcetes (54; r.294-288 BC; d.283 BC) at the Battle of Gaza (312 BC) enabled Seleucus to return to Babylonia, an event that marked the beginning of the Seleucid Dynasty.
In 307 or 305 BC Seleucus founded the first capital of the Seleucid Empire at Seleucia on the west bank of the Tigris, opposite the smaller town of Opis (later Ctesiphon). Seleucia grew to economic importance and ended the dominance of Babylon. Antigonus’ defeat and death at Ipsus (301 BC) gave the Seleucids access to the Mediterranean through northern Syria and Cilicia. When in c.300 BC Seleucus founded the city of Antioch on the eastern side of the Orontes, the Seleucid Empire became essentially a Syrian kingdom.
The Seleucids remained in control of Mesopotamia until the country west of the Tigris was temporarily lost to Molon (d. 220 BC), the Seleucid satrap of Media. In 221 BC Antiochus III the Great (c.54; r.223-187 BC) moved against him from Syria and the revolt collapsed.
Mithridates-I of Parthia (c.57; r.171-138 BC) conquered Seleucid territory in Iran and entered Seleucia in 141 BC. An attempt in 140/139 BC by Demetrius II (r.145-138, 129-126 BC) to recover lost territories failed and he was taken prisoner by the Parthians. Antiochus VII (r.138-129 BC) attacked the Parthians and briefly took back Mesopotamia and Media before being ambushed and killed by Phraates II of Parthia (43; r.138-128 BC). This marked the end of Seleucid rule in Mesopotamia and the beginning of the small principalities.
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