After unifying the region with his kingdom in the early 8th century BC, king Argishtis I of Urartu resettled many of its inhabitants in his newly built city of Erebuni (modern day Armenian capital Yerevan).

After Alexander the Great's campaigns in the 330s BC and the subsequent collapse of the Achaemenid Empire, Sophene remained part of the newly independent kingdom of Greater Armenia.

Following Antiochus' defeat by the Romans at the Battle of Magnesia in 190 BC, both Zariadres and Artaxias declared themselves independent kings.

Zariadres and his descendants ruled the Kingdom of Sophene until it was reunified with Greater Armenia by Tigranes the Great in the 80s BC.

Branches of the Orontid dynasty continued to rule parts of Sophene after it was annexed by Greater Armenia.