He was on Caesar's side during the Civil War with Pompey. During the campaign in Greece, Caesar sent Domitius with two legions to intercept Metellus Scipio who was bringing the Syrian legions to Pompey. At the decisive Battle of Pharsalus he commanded the centre of Caesar's army. After the battle he became governor of Asia. He tried to oppose the invasion of Pharnaces, the king of Bosphorus, who had taken the occasion of the Roman civil war to invade the province of Pontus; however, he suffered a crushing defeat at the Battle of Nicopolis in Armenia (December of 48 BC). Direct intervention by Caesar brought a quick end to the conflict, and Pharnaces' army was annihilated at Zela in 47 BC. Despite this failure, he remained a trusted friend of Caesar.