Seven years have passed since Antony's departure from Rome, and the former commander, dissipated and debauched - held in thrall by the charms and sexual prowess of his new bride, Cleopatra, withholds precious shipments of grain from Rome, where people die in the streets from hunger. Unable to incite a war with Antony and Egypt without committing political suicide, Octavian sends Atia and Octavia to Alexandria to mediate and reason with Antony; a strategy which proves predictably unsuccessful. However, former Roman senator Posca and his wife, Jocasta, flee Alexandria with Atia and Octavia to Rome where he provides Octavian with all the ammunition he needs to bring about a war with Antony and Cleopatra. Meanwhile, Pullo has taken over the Avantine gangs of Rome. But later, a fatal blow is stricken to the torrid affair that has continued between Pullo and Gaia, as karmic debt comes to call when she saves him from the sadistic Memmino, but gets fatally wounded, and she lets it slip to Pullo that she was the one who poisoned Eirene. Octavian asks Pullo to join him in the campaign against Egypt, and Pullo agrees without question, hoping to reunite and redeem his blood brother, Vorenus, who continues to stand by Antony's side despite his growing contempt for his commander. Octavian calls for war against Antony in the Senate, and is met with thunderous approval.

With the defeat of the Egyptian fleet at Actium, Mark Antony and Cleopatra retreat to their palace and await their fate. Believing that Cleopatra has taken her life, Mark Antony decides follow her into the afterlife. She has other plans however and is quite prepared to negotiate with Octavian if there is any possibility her life and those of her children will be spared. Cleopatra asks Vorenus to take her son Caesarian to safety and Octavian sends Pullo after them. The old friends are soon together again but are waylaid by bandits. With Vorenus severely wounded, Pullo takes him back to Rome for what he hopes will be a happy reunion with his children.