In Gaul in 52 B.C., two Roman soldiers, Legionary Titus Pullo and Centurion Lucius Vorenus, are tasked with recovering Julius Caesar's personal Eagle, stolen from his camp in the dead of night. With his campaign in Gaul coming to a successful conclusion, Caesar's popularity is continuing to grow. He's saddened however when he receives news from his good friend Pompey Magnus that his daughter, Pompey's wife, has died in childbirth. In the Senate, Pompey must defend the prolonged absence of his friend and co-Consul Caesar against charges of corruption and of waging an illegal war. It's all a ruse however as he is plotting to eliminate him. Meanwhile, Atia of the Julii sends her son Octavian to Gaul deliver a gift of a beautiful stallion to his great uncle Julius Caesar. He is taken prisoner along the way. Fortunately, Vorenus and Pullo rescue him and as a result, both receive Caesar's favor.

Caesar winters his army in Gaul near the Italian border while his enemies in Rome fear that he will do something no Roman General has done: cross the Rubicon with his army. To counter-balance his opponents, Caesar puts his friend Mark Antony up for office as the people's Consul. Vorenus and Pullo accompany Mark Antony and Octavian to Rome. For Pullo, it's an opportunity to get drunk and ravish every woman in sight. He also loses all of his money in a crooked dice game leading to a major brawl. For Vorenus, he will have a reunion with his wife Niobe who he has not seen for 8 years. He's told that the baby he finds in his home is his grandson but Niobe is hiding a secret. In the Senate, there is a move to have Caesar declared a traitor but when Mark Antony tries to return to the Senate to veto their decision, Pullo is attacked by someone he fought the night before. Antony thinks the attack is against him and Pullo kills the man and Caesar declares Pullo a hero.

With Caesar quickly advancing toward Rome, Pompey begins ordering a retreat and forces his citizens to pick sides. Timon does Atia's dirty work and Vorenus cannot understand why no one is resisting while on a scouting mission.

Atia and her family have stayed behind when Pompey and others fled and she now throws a party for her triumphant uncle, Julius Caesar. She clearly has her sights set on the great leader and is puzzled when he sends her a guest list that includes Servilia of the Junii. She soon finds out why. Pompey wants to find out what happened to the gold from the Roman Treasury and sends his son Quintus to Rome to find out what happened. They go directly to Vorenus' home but he has no idea what they are talking about. Pullo arrives however and Vorenus tells him to go directly to Caesar himself and explain. Octavian meanwhile learns of one of his uncle's secrets.

Caesar contemplates Pompey's counteroffer. Vorenus continues to struggle as a businessman and must reevaluate his career choice. Atia schemes to come between Caesar and Servilia and Pullo seeks Octavian's help.

Caesar pursued Pompey to Greece but the tide has turned and it's Caesar who is on the run. He contacts Mark Antony, who he left in charge in Rome, to come and join him with the 13th Legion but Antony seems to be in no hurry. Vorenus has re-enlisted in Antony's Legion and he and Niobe have begun to renew their marital relationship. The presence of Niobe's sister is the only sour note in their house. Pullo meanwhile continues to train young Octavian in the use of arms and the boy's mother Atia is so pleased with his development that she decides he should take another step to manhood and orders Pullo to take him to a brothel so he can have his first sexual experience. Atia also continues with her scheming ways and believing that Caesar is done for, decides she had better make friends with Servilia.

Rejected by Vorenus and Eirene and racked by guilt for the killing of Eirene's fiancé out of a jealous rage, Pullo has sunk to working as an assassin for the gangster Erastes. When Pullo gets arrested for killing one of Caesar's popular opponents, he condemns himself by refusing to name who hired him, despite Octavian's attempts to defend him. Meanwhile, Vorenus finds his new official duties as magistrate tedious, especially when he gets caught between Caesar and the demands made by veterans' spokesman Mascias. Niobe revels in the prestige of Vorenus's office until Caesar invites the Voreni to a symposium at Atia's house. Despite Servilia's surreptitious propaganda depicting Brutus as a tyrant-killer, and the urgings of Cassius and his own doubts, Brutus resists turning against Caesar. Antony makes his move to win back Atia. On the point of death in a gladiator arena, Pullo finds a new reason to live that yet again puts Vorenus in a tight spot. Also, Caesar makes a move that compels the conflicted Brutus to make up his mind to turn against Caesar.

In the wake of Caesar's death, Mark Antony considers a move north, while Vorenus issues a curse he soon regrets.

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.

Lucius Vorenus, the power-hungry "Son of Hades", controls the Aventine but practices a pointless, beastly reign of terror, coming down hard on gang captains for futilities, and nearly ruins his friendship with Pullo, whose efforts to calm things down are mistaken for disrespect and disobedience, even starts a fight once he learns the truth about Niobe; Pullio leaves Rome disgusted. After Atia convinces Marc Antony the governorship of ghastly Macedonia after his consulate would not only be unpleasant but leave him exposed to his dangerous enemies, he puts the heat on senatorial leader Cicero to give him Gaul instead, which once was the base for Julius Caesar's coup d'état. The slave Duro endures male prostitution but most arrogantly demands extra pay and even a kiss from Servilia as it will take more time to commit the planned murder in Atia's home. Marc promises Atia not to hurt Octavian, whose recruiting he calls a joke, after putting down his party's expected plot. Brutus has a hard time controlling himself while soliciting the Bithynian king's financial support to raise an army. Instead of proposing Antony for governor of Gaul, Cicero sends an extremely insulting speech and joins Octavian's growing army.

Having learned that Vorenus' children are alive, Pullo sets off to find him in Gaul where he is again a serving soldier in Mark Antony's army. He had hoped to arrive before Octavian and Antony's armies meet in battle. Too late however, he is forced to find what is left of Antony's army in the mountains. He finds Vorenus alive and well, if somewhat battle worn, and they set off to find the children. The victorious Octavian plans his return to Rome. In Western Turkey, Brutus and Cassius amass their own army, now 9 Legions strong. In Rome, Servilia's attempt to kill Atia fails and Atia has her kidnapped tortured beyond what even her henchman Timon can stand.

Vorenus and Pullo return to the Collegium in Rome with Vorenus' family, but some of the "changes" that Pullo had warned him about regarding his two daughters Vorena both the Elder and Younger, as well as his wife's son, begin to manifest themselves into hostility and resentment. But Vorenus is completely oblivious to this, and is too blissfully happy to return to the role of 'father'. Meanwhile, Octavian finally returns and manages to negotiate the Senate Consul's seat from a scheming Cicero, but in spite of his promise to 'faithfully follow' the older man's counsel, Octavian proves that he certainly has a mind of his own, vowing to hunt down and kill the assassins of Julius Caesar, much to Cicero's consternation. Elsewhere, Brutus and Cassius receive news that might prove useful in staging a triumphant return to Rome, as well as the ultimate defeat of both Mark Antony and Octavian's forces. Also, Atia has a reunion with her son that is strained to say the least, but there is a tentative reconciliation between them. And another, much less stressful reunion between two lovers, Octavia and Agrippa, who saves her from an attempted date-rape at an orgy party, will bring about an unforeseen alliance between two formerly mortal enemies.

Inconsolable at the death of Brutus at Philippi, Servilia makes her final bid to gain the ultimate vengeance against Atia. Meanwhile, Eirene and Gaia have a major falling-out, prompting Eirene to demand that Pullo properly chastise the slave. When he does, the dynamic between the two of them changes in a violent and unexpected fashion. King Herod engages Mark Antony as a reluctant ally by offering a generous gift of 20,000 pounds of gold, and when Posca is excluded from sharing in the windfall, he engineers a move behind-the-scenes that will once again strain the uneasy truce between Octavian and Antony. Vorenus eldest daughter, Vorena, is blackmailed by Mascius into spying on her father after her tryst with one of his men is discovered. The end of two love affairs and a marriage in the house of Julii have major ramifications for life in the city and on the Aventine when Octavian insists on the courtship between Octavia and Mark Antony which irks both Atia and Agrippa. Also, a desperate move to assassinate Herod finishes the relationship between contentious siblings Timon and Levi when they have a falling out, and Levi gets killed by accident.

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.