Euthydemus was allegedly a native of Magnesia and possible Satrap of Sogdiana, who overturned the dynasty of Diodotus of Bactria and became a Greco-Bactrian king in about 230 BC according to Polybius. Strabo, on the other hand, correlates his accession with internal Seleucid wars in 223/221 BC.

Little is known of his reign until 208 BC when he was attacked by Antiochus III the Great, whom he tried in vain to resist on the shores of the river Arius, the modern Herirud. The war lasted three years, and Euthydemus was besieged in his capital Bactra (modern Balkh). But Antiochus saw that he was not able to subdue Bactria and Sogdiana, and so in 206 concluded a peace with Euthydemus, in which he recognized his legitimacy, also promising to betroth one of his daughters to Euthydemus' son Demetrius.

His death has been estimated to about 200 BC.

There exist many coins of Euthydemus, portraying him as a young, middle-aged and old man. Some of them could be memorative issues by his son and a later king, Agathocles. The attribution of some of his coins (the younger portraits) to a second Euthydemus has been suggested but the evidence is very vague. The end of his reign can not be fixed, but he was succeeded by Demetrius, who went on to conquer northern India.