The Seleucid Empire became a major center of Hellenistic culture – it maintained the preeminence of Greek customs where a Greek political elite dominated, mostly in the urban areas. The Greek population of the cities who formed the dominant elite were reinforced by immigration from Greece. Seleucid expansion into Anatolia and Greece halted abruptly in the early 2nd century BC after decisive defeats at the hands of the Roman army. Seleucid attempts to defeat their old enemy Ptolemaic Egypt were frustrated by Roman demands. Having come into conflict in the East (305 BC) with Chandragupta Maurya of the Maurya Empire, after several defeats, Seleucus I entered into an agreement with Maurya whereby he ceded vast territory west of the Indus, including the Hindu Kush, modern-day Afghanistan, and the Balochistan province of Pakistan and offered his daughter in marriage to the Maurya Emperor to formalize the alliance.
Antiochus III the Great attempted to project Seleucid power and authority into Hellenistic Greece, but his attempts were thwarted by the Roman Republic and by Greek allies such as the Kingdom of Pergamon, culminating in a Seleucid defeat at the 190 BC Battle of Magnesia. In the subsequent Treaty of Apamea in 188 BC, the Seleucids were compelled to pay costly war reparations and relinquished claims to territories west of the Taurus Mountains. The Parthians under Mithridates I of Parthia conquered much of the remaining eastern part of the Seleucid Empire in the mid-2nd century BC. However, the Seleucid kings continued to rule a rump state from Syria until the invasion by Armenian king Tigranes the Great in 83 BC and their ultimate overthrow by the Roman general Pompey in 63 BC.
Contemporary sources, such as a loyalist degree from Ilium, in Greek language define the Seleucid state both as an empire (arche) and as a kingdom (basileia). Similarly, Seleucid rulers were described as kings in Babylonia.
Starting from the 2nd century BC, ancient writers referred to the Seleucid ruler as the King of Syria, Lord of Asia, and other designations; the evidence for the Seleucid rulers representing themselves as kings of Syria is provided by the inscription of Antigonus son of Menophilus, who described himself as the "admiral of Alexander, king of Syria". He refers to either Alexander Balas or Alexander II Zabinas as a ruler.
Alexander, who quickly conquered the Persian Empire under its last Achaemenid dynast, Darius III, died young in 323 BC, leaving an expansive empire of partly Hellenised culture without an adult heir. The empire was put under the authority of a regent in the person of Perdiccas, and the territories were divided among Alexander's generals, who thereby became satraps, at the Partition of Babylon, all in that same year.