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.

As they try to reach Caesar in Greece, the shipwrecked Vorenus and Pullo confront an unexpected dilemma. Back in Rome, Atia again sends Octavia to beg protection from Servilia, who complies readily to encourage her growing friendship with Octavia. As they prepare their counterattack against Caesar, Pompey's Republicans begin to squabble over both the anticipated spoils and the method of finishing Caesar off. Niobe's sister Lyde comes back to see her and comforts her over Vorenus's disappearance. Badly outnumbered, Caesar and Antony make their stand at Pharsalus. On his arrival in Egypt, Pompey is greeted by a Roman veteran.

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.

The defeated Cato and Scipio fall back on the African city of Utica after the Battle of Thapsus where they decide to end it all. Caesar, after two years of fighting in Greece and Egypt, returns to Rome and receives a hero's welcome. Meanwhile, Servilia's cold rage against the Julii clan makes Brutus's submission to Caesar even more painful. Octavian returns home from military school and Caesar, impressed with his nephew's incisive political acumen, appoints him a pontiff despite his youth. Having opened and operated a profitable butcher shop, Niobe and Lyde get the reluctant Vorenus and Pullo to join the trade, but Vorenus again crosses paths with the thug Erastes, now the crime lord of the Aventine. Learning of Caesar's secret "affliction," Servilia persuades her lover Octavia to cajole her brother into revealing more, but she only learns Niobe's secret instead. Servilia motivates Octavia to try again by other means, with dreadful consequences for both sister and brother. Pullo's affection for his slave Eirene deepens. Enraged at Servilia's manipulation of her children, Atia enlists Timon and his band of thugs to retaliate, thus escalating the term 'catfight' to a very different level.

The price of Caesar's mercy: Cicero nominates Caesar to an unprecedented ten-year dictatorship and Brutus speaks in support of the motion. With martial authority and Niobe at his side, Vorenus campaigns for magistrate under Posca's advice, but is shocked to learn from Posca that Caesar has already fixed the election in Vorenus's favor. Meanwhile, Atia continues her humiliation of Servilia while denying any involvement in her assault. But Atia becomes troubled by the silent depression of Octavia after Octavian compels her to return home from the cloister where she had fled. As Servilia lies at home shattered by her recent attack, she soon revives and gets her self-confidence back when she takes in the homeless and embittered Quintus Pompey whom she sees as her tool for revenge against Caeser for leaving her. As Caesar prepares for his Triumph involving five days of celebration and games, Antony finds that the dictator has no sense of humor about the trappings of power. The circulation of a denunciation of Caesar, signed by Brutus, fascinates Rome but stuns Brutus, who suspects his mother. Denied permission to march with the Thirteenth in the Triumph, the dejected Pullo resolves to make a new life as a civilian with Eirene, but his dream leads only to horror for the Vorenii and utter wretchedness for himself.

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.

Vorenus' defense of Caesar lands him in an unexpected position of power within Rome. Meanwhile, Servilia hurls the final obstacle in her ambitious and complex revenge plan against Atia.