After Caesar's return to Rome, he celebrated four triumphs: over Gaul, Egypt, Asia, and Africa. Caesar, however, left for Spain in November 46 BCE, to subdue opposition there. His appointment of Quintus Cassius Longinus after his first campaign in Spain had led to a rebellion: Cassius's "greed and... unpleasant temperament" led to many provincials and troops declaring open defection to the Pompeian cause, in part rallied by Pompey's sons Gnaeus and Sextus. The Pompeians there were joined by other refugees from Thapsus, including Labienus.

After receiving bad news from the peninsula, he left with a single experienced legion, as many of his veterans had been discharged, and put Italy in the hands of his new magister equitum Lepidus. He led eight legions in total, which gave rise to fears that he might be defeated by Gnaeus Pompey's formidable force of more than thirteen legions and further auxiliaries. The Spanish campaign was replete with atrocities, with Caesar treating his enemies as rebels; Caesar's men adorned their fortifications with severed heads and massacred enemy soldiers.

Caesar first arrived in Spain and relieved Ulia from siege. He then marched against Corduba, garrisoned by Sextus Pompey, who requested reinforcements from his brother Gnaeus. Gnaeus at first refused battle at Labienus' advice, forcing Caesar into a winter siege of the city, which was eventually called off after little progress; Caesar then moved to besiege Ategua, shadowed by Gnaeus' army. Substantial desertions, however, started to take their toll on the Pompeian forces: Ategua surrendered on 19 February 45 BCE, even after its Pompeian commander massacred suspected defectors and their families on the walls. Gnaeus Pompey's forces retreated from Ategua afterwards, with Caesar following.