Domitius Calvinus came from a noble family and was elected consul for 53 BC, despite a notorious electoral scandal.
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.
Domitius Calvinus's activities immediately after the death of Caesar are unknown, but in 43 BC he was a strong supporter of Octavianus and participated in the civil war against Brutus and Cassius.
During the Philippi campaign in 42 BC, he had to bring reinforcements from Italia to Greece for Mark Antony and Octavianus' army, however, his fleet was destroyed by the enemy in the Ionian Sea with the loss of two legions.