Antiochus I Soter ( 324/323-262/261 BC reigned 281 BC - 261 BC) was half Persian, his mother Apame being one of those eastern princesses whom Alexander had given as wives to his generals in 324 BC.

On the assassination of his father Seleucus I in 281 BC, the task of holding together the empire was a formidable one, and a revolt in Syria broke out almost immediately. With his father's murderer, Ptolemy, Antiochus was soon compelled to make peace, abandoning apparently Macedonia and Thrace. In Asia Minor he was unable to reduce Bithynia or the Persian dynasties that ruled in Cappadocia.

In 278 BC the Gauls broke into Asia Minor, and a victory that Antiochus won over these hordes is said to have been the origin of his title of Soter (Gr. for "saviour").

At the end of 275 BC the question of Palestine, which had been open between the houses of Seleucus and Ptolemy since the partition of 301 BC, led to hostilities (the "First Syrian War"). It had been continuously in Ptolemaic occupation, but the house of Seleucus maintained its claim.

War did not materially change the outlines of the two kingdoms, though frontier cities like Damascus and the coast districts of Asia Minor might change hands.

About 262 BC Antiochus tried to break the growing power of Pergamum by force of arms, but suffered defeat near Sardis and died soon afterwards (262 BC). His eldest son Seleucus, who had ruled in the east as viceroy from 275 BC(?) till 268/267 BC, was put to death in that year by his father on the charge of rebellion. He was succeeded (261 BC) by his second son Antiochus II Theos.