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In January 49 BCE, Metellus Scipio persuaded the senate to issue the ultimatum to Caesar that made war inevitable. That same year, he became proconsul of the province of Syria. In Syria and in the province of Asia, where he took up winter quarters, he used often oppressive means to gather ships, troops, and money:
He put a per capita tax on slaves and children; he taxed columns, doors, grain, soldiers, weaponry, oarsmen, and machinery; if a name could be found for a thing, that was seen as sufficient for making money from it.
Scipio put to death Alexander of Judaea, and was acclaimed Imperator for "alleged" victories in the Amanus Mountains — as noted disparagingly by Caesar.
In 48 BCE, he brought his forces from Asia to Greece, where he manoeuvred against Gnaeus Domitius Calvinus and Lucius Cassius until the arrival of Pompeius. At the Battle of Pharsalus, he commanded the centre. After the optimates' defeat by Caesar, Metellus fled to Africa. With the support of his former rival-in-romance Cato, he wrested the chief command of Pompeius's forces from the loyal Attius Varus, probably in early 47 BCE. In 46 BCE, he held command at the Battle of Thapsus "without skill or success," and was defeated along with Cato. After the defeat, he tried to escape to the Iberian Peninsula to continue the fight, but was cornered by the fleet of Publius Sittius. He committed suicide by stabbing himself so he would not fall into the hands of his enemies.