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.
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.
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.
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.
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.
Picking up exactly where Season One left off on the Ides of March, 44 BC, Caesar has been assassinated, stabbed to death, and his bloody corpse lays in the senate. The rapidly spreading news shocks the city. Even consul Marc Antony must run to the safety of Atia's house where he swears to take bloody revenge on Caesar's murderers, but for the time flees with Caesar's family to the north. But Octavian keeps a cooler head then his mother. Calpurnia insists on the private reading of Caesar's will, which names Gaius Octavian as his adopted son and full heir and makes a gift to each citizen while freeing Posca (the slave who reads it out) with a stipend, but they must fear a rightful tyrannicide will be declared allowing full confiscation. Octavian points out legally declaring Caesar a tyrant would also invalidate all his deeds, including mandates held from him, so Brutus' followers have an interest in a full pardon instead. Hearing about Vorinus accidental killing of Niobe, Pullo rushes to his aid. Meanwhile, Cicero first congratulates Brutus's side, then pays his respects to surprise visitor Marc Antony who presses Octavian's legal logic means elections are necessary, claims Caesar's popular following and offers stability by a deal: Caesar is to be given a state funeral, the republic simply resumes and all terms of office continue. Despite Cicero's suggestion to kill Antony instead, Brutus accepts. Romans massively attend Caesar's funeral pyre; after the speeches, Brutus who was too cerebral is clearly out of popular favor, inspiring retort Marc Antony in. Elsewhere, Vorenus reclaims his children with Pullo, and kills Flavio and his master who admits having raped and killed them.
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 loosing 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.
Servilia's plan to assassinate Atia backfires, with horrific circumstances when Atia's servant Althea accidentally tastes a bowl of poisoned stew before Atia samples it. Atia has Timon and his men abduct Servilia and subject her to hours of physical and degrading torture. But the brutal punishment Atia desires against her mortal enemy is one too many atrocities for Timon, who finally snaps, frees the physically and emotionally broken Servilia, and ends his contentious relationship with Atia at the advice of his brother Levi. In Gaul, with help from the grown-up Octavian, Titus Pullo seeks out Lucius Vorenus on the bloody battlefields where Octavian's armies have nearly wiped out the rebel Marc Antony's legions. Once he finds Vorenus, Pullo sets off with his friend to find and rescue Vorenus' family, sold into slavery. Charged with hand-delivering a message to Octavia, a love-struck Agrippa jumps at the chance to see her again. Meanwhile, Cicero balks at the news that Octavian is returning with his legions to Rome, and leaving the bloodied, but unbeaten, Antony's forces ready to fight another day. In a remote province in Asia Minor, Brutus continues building his own army to retake Rome and destroy both Octavian and Anthony's forces. Working together again as friends and "brothers", Titus and Lucius accomplish their urgent mission with a little intimidation and violence against the slave mine procurator.
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.
Cicero is finally undone by his duplicity in the form of Titus Pullo, acting upon Octavian's request to assassinate all supporters of Brutus in Rome. Pullo and Vorenus enjoy a happy if counterfeit outing with their families in the countryside to hide their assassin mission. Vorena the Elder's dangerous dalliance with one of Mimeo's men continues, and the torrid affair between Octavia and Agrippa escalates. Atia's casual cruelty to ask for the assassination of people she doesn't like results in complete disaster for Octavia's friend Jocasta. Elsewhere, the headstrong Levi engages Timon in a plan to assassinate King Herod by recruiting in the synagogue where they worship. Disastrously out manned, Brutus and Cassius engage the combined legions of Mark Antony and Octavian, and confront their fates in the ferocious battle at Philippi.
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.
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.