Brutus gets a chilly reception from Servilia when he returns home from Greece. In Egypt, Caesar rebukes the advisers of the boy king, Ptolemy XIII, for their presumption in eliminating Pompey and demands the man who killed him. Caesar decides to intervene in the dispute between Ptolemy and his sister-wife, Cleopatra, to ensure both Rome's grain supply and his own access to Egypt's treasure. Antony, in an unusual show of prudence, advises against this with only half a legion in Alexandria and Cato and Scipio still at large in Africa. Caesar sends Vorenus and Pullo to rescue Cleopatra from house-arrest and escort her to Alexandria. Upon meeting Vorenus and Pullo, the narcissistic, opium-smoking teenage Cleopatra decides that her only hope of survival is to seduce Caesar and she compels Vorenus and Pullo to help smuggle her into the city first by unsuccessfully attempting to seduce Vorenus, but she has better luck with Pullo. Servilia's relationship with Octavia deepens beyond friendship into a passionate lesbian tryst. Caesar is besieged in Alexandra by the Egyptians loyal to Ptolemy. Back in Rome, Antony greets Brutus and Cicero on the floor of the deserted Senate and makes Cicero a promise to kill him if he ever turns against him.

Even though his wife and children are avenged by the Erastes killing, Lucius Vorenus keeps mourning for over a month till Pullo gets Marc Antony who scolds him for Caesar's death and the continuing bloody Aventine gang riots that have resulted in the gangs wanting to fill the void left by Erastes sudden demise. Octavian is losing patience with Marc Antony for payment of Caesar's inheritance. Meanwhile, Queen Cleopatra of Egypt arrives in Rome to pay her respects to Caesar and she also negotiates with Antony's military protection for her Pharaonic throne in exchange for valuable grain shipments. But she gets dismissed as a whore when she demands that her four-year-old son, Caesarion, be recognized as Caesar's legal son. Yet the uninvited pair of them is welcomed by Antony at Atia's party. Abusing a truce in the name of the goddess Concord and smashing up her statue, Vorenus imposes as 'son of Hades' on the gang captains a peace, paid off by Antony so trade and politics on and near the Aventine no longer get disrupted. After his mother Atia and sister Octavia tell him to accept Antony denying Caesar's legacy and laugh at his ambition to provide Rome the leadership it needs, Octavian borrows against his vast inheritance to buy popularity by paying for Caesar's lavish bequests to the populace; Antony violently refuses a political deal with him. Octavian then leaves home and retires to Campania with General Agrippa. Cicero and Brutus' mother, Servilia, hope this strife among the Julii clan will allow their party to return to Rome. Also, Timon's long-lost brother, Levi, arrives back in Rome wanting his help to make a new life for himself.

Octavian takes a new bride, Livia, and then introduces her to his family in a startling way... by having her witness the punishment he metes out to Atia and Octavia, for secretly defying the social constraints established through the facade of Octavia's "marriage" to Mark Antony. The vengeful Gaia carries out her plan to poison Eirene, which produces most dire consequences for Pullo, and no one else is the wiser. Meanwhile, Octavian, Antony, Maecenas, and their associates barely maintain their relationships of congenial contempt and hypocrisy, as everyone tries to figure out who has duped whom with the disappearance of the gold that was Herod's 'gift.' Now forced by Octavian to leave Rome to serve as an 'ambassador' to Egypt, Antony defies the conditions of Atia's house arrest to bid her a bittersweet farewell. The same can be said of Agrippa, who learns some startling news as he severs his relationship with Octavia. Timon also decides to move with his family to Judia to start a new life over for themselves. With the theft of the gold, Lucius and Pullo suspect and accuse a badly-wounded Mascius of having engineered a double-cross, but the real traitor of Vorenus' gang comes to shocking light which is the eldest Vorena. Now having pinpointed Memmio as the real culprit, Pullo takes the group to meet for a parlay with the devious captain and his cohorts, resulting in swift and bloody retribution for the traitors. A despondent Vorenus, his family fractured once again, begs Antony to allow him to come to Egypt, and finds his offer grudgingly accepted. Antony returns to Egypt and is reunited with the seductive Cleopatra.

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.