Literary sources, notably Polybius, record how he and his son Demetrius resisted an invasion by the Seleucid king Antiochus III from 209 to 206 BC.

Euthydemus expanded the Bactrian territory into Sogdia, constructed several fortresses, including the Derbent Wall in the Iron Gate,[2] and issued a very substantial coinage.

He then successfully resisted a three-year siege in the fortified city of Bactra, before Antiochus finally decided to recognize the new ruler, and to offer one of his daughters to Euthydemus's son Demetrius around 206 BC.

Antiochus, on receiving the young man and judging him from his appearance, conversation, and dignity of bearing to be worthy of royal rank, in the first place promised to give him one of his daughters in marriage and next gave permission to his father to style himself kingPolybius also relates that Euthydemus negotiated peace with Antiochus III by suggesting that he deserved credit for overthrowing the descendants of the original rebel Diodotus, and that he was protecting Central Asia from nomadic invasions thanks to his defensive efforts.

The war lasted altogether three years and after the Seleucid army left, the kingdom seems to have recovered quickly from the assault.

Polybius claims that Euthydemus justified his kingship during his peace negotiations with Antiochus III in 206 BC by reference to the threat of attack by nomads on the Central Asian steppe: Archaeological evidence from coin finds shows that Euthydemus' reign saw extensive activity at fortresses in northwestern Bactria (the modern Surkhan Darya region of Uzbekistan), especially in the Gissar and Köýtendag mountains.

The Seleucid fortress at Uzundara was expanded and large numbers of Euthydemus' bronze coins have been found there, as was as hundreds of arrowheads and other remains indicating a violent assault.

[10] However, Stančo also notes that Derbent wall seems to have been designed not to defend against an attack from Sogdia to the northwest, but from Bactria to the southeast.

Stančo proposes that Euthydemus was originally based in Sogdia and built the fortifications to protect himself from Bactria, before seizing control of the latter.

[11] Lucas Christopoulos goes further, proposing that he controlled a large area going from Sogdiana to Gansu and the Tarim basin walled cities together with enrolled Hellenized Saka horsemen even before he ascended the throne of Bactria in 250-230 BC.

[12] In an inscription found in the Kuliab area of Tajikistan, northeastern Greco-Bactria, and dated to 200-195 BC,[13] a Greek by the name of Heliodotus, dedicating an altar to Hestia, mentions Euthydemus as the greatest of all kings, and his son Demetrius I:[14] This is a further indication, alongside the passages from Polybius, that Euthydemus had made his son Demetrius a junior partner in his rule during his lifetime.

He produced significantly more coins than any of his successors and was the last Greco-Bactrian coinage to include gold denominations until the time of Eucratides I (ca.

[18] Heracles was apparently a popular deity in Bactria, associated with Alexander the Great, but this reverse type is very similar to coins minted by the Seleucids in western Asia Minor, near Euthydemus' home city of Magnesia.

The first of these is an 'idealising' portrait, depicting him as a young or middle-aged man, with very large eyes, an arching eyebrow, pointed nose and protruding chin, the diadem is very broad.

Finally, in the fourth portrait style, Euthydemus is portrayed as a visibly aged man with very large jowls; his hair also interacts with the diadem in a more natural way.

[29]The earliest coins use portrait type 1 and have a 6 o'clock die axis (i.e. the top of the obverse is aligned with the bottom of the reverse).

Almost all have a bearded male head, identified as Heracles, on the obverse and a rearing horse on the reverse with the legend ΒΑΣΙΛΕΩΣ ΕΥΘΥΔΗΜΟΥ ('of King Euthydemos').

Lyonnet proposes that these coins were produced by refugees fleeing the destruction of the Greco-Bactrian kingdom by the Yuezhi in the mid-second century BC.