The Seleucid Empire, a Greek power in West Asia during the Hellenistic period, was established in 312 BCE by Seleucus I Nicator, a Macedonian general. This empire emerged following the division of Alexander the Great's Macedonian Empire and was ruled by the Seleucid dynasty until its annexation by the Roman Republic in 63 BCE. Seleucus I initially received Babylonia and Assyria in 321 BCE and expanded his territory to include modern-day Iraq, Iran, Afghanistan, Syria, Lebanon, and parts of Turkmenistan, regions once controlled by the Achaemenid Empire. At its peak, the Seleucid Empire also encompassed Anatolia, Persia, the Levant, Mesopotamia, and modern Kuwait.

The Seleucid Empire was a significant center of Hellenistic culture, promoting Greek customs and language while generally tolerating local traditions. A Greek urban elite dominated its politics, supported by Greek immigrants. The empire faced challenges from Ptolemaic Egypt in the west and lost significant territory to the Maurya Empire in the east under Chandragupta in 305 BCE.

In the early 2nd century BCE, Antiochus III the Great's efforts to extend Seleucid influence into Greece were countered by the Roman Republic, leading to the loss of territories west of the Taurus Mountains and significant war reparations. This marked the beginning of the empire's decline. Parthia, under Mithridates I, seized much of its eastern lands in the mid-2nd century BCE, while the Greco-Bactrian Kingdom thrived in the northeast. Antiochus' aggressive Hellenizing (or de-Judaizing) activities provoked a full scale armed rebellion in Judea—the Maccabean Revolt. Efforts to deal with both the Parthians and the Jews as well as retain control of the provinces at the same time proved beyond the weakened empire's power. Reduced to a smaller state in Syria, the Seleucids were eventually conquered by Tigranes the Great of Armenia in 83 BCE and finally by the Roman general Pompey in 63 BCE.