Season two's storyline picks up right where season one left off: with the 44 B.C. assassination of Gaius Julius Caesar and the near-simultaneous death of Niobe, wife of Caesar's faithful bodyguard Lucius Vorenus. Diverted from his post after learning that Lucius, his assumed grandson, was in fact Niobe's illegitimate son, Vorenus now descends into near-madness over his failure to protect Caesar, his role in his spouse's death, and the rumored murder of his estranged daughters.
Things pick up shortly after Caesar's murder. Octavian wants to keep his family from fleeing the city so he devises a plan. News of this makes Antony happy so he tells Brutus. Vorenus mourns Niobe's death but casts aspersions upon his children.
Cleopatra arrives in Rome to pay her homage to Caesar, and to seek legitimization for Caesarion. Egypt's queen causes further complications between Anthony and Atia, who still struggles with Servilia. Timon's brother arrives from Jerusalem. The death of Erastes throws the underworld, and Rome's river commerce into chaos, and Pullo and Vorenus step into the gap. Octavian and Anthony begin a long and bitter rivalry with a dispute over Caesar's will and sharing of power.
Brutus and Cassius struggle to raise foreign armies to oppose the Cesarean party. Mark Antony's plans to change his post-consul proconsular governorship from Macedonia to Gaul are derailed when Cicero delivers an in-absentia message to the Senate, and throws his support behind Octavian. Vorenus struggles to contain an all-out gang war in the Aventine Collegium, of his own making,that he blames on Pullo. In the house of the Julii, Octavia passes the hours in a drug induced daze, while a duplicitous youth named Duro, planted amongst the Julii by Servilia, looks for the chance to set a deadly plan in motion.
Pullo races to find Vorenus with news of his family's fate. Servilia's plans to eliminate a rival exact a high price from her. Cicero is astonished when Octavian sends word that his victorious legions are coming home to Rome. In Rome, Timon finally grows weary of Atia's bidding.
Despite Pullo's advice, Vorenus and his family return to the Collegium with his family who is reunited, and cleansed of their ordeal. Octavian is denied a triumph and urges Cicero to endorse his bid to be made Consul in exchange for an agreement to allow Cicero to veto his actions. Octavian takes both Cicero and the Senate by surprise with his first Consular act. Vorenus attempts' to make peace with Memmio and Cotta create suspicions that he has gone soft.
Vorenus receives orders to plunge Rome into a bloodbath the likes that have not been seen since the dictatorship of Sulla. Octavia reveals her secret to Atia, and the armies of the Liberators and the Caesarians clash for the last time, with the fate of Republic in the balance.
Antony's nature reasserts itself, and challenges his alliance with Octavian. Timon and Levi set themselves against Herod's plans. Servilia's public displays of grief leave Atia unsettled. Gaia uses Pullo's punishment as a weapon against him. His daughter's sudden interest in business matters arouses Vorenus' suspicions. Posca gets married.
Octavian proclaims a new era of virtue in Rome, a program that his family and subordinates find impossible to obey. Vorenus is sent on a mission after a missing shipment of gold to discover who mysteriously hijacked it on its way to the Roman treasury. Pullo's loss and rage are channeled against Memmio, Omnipor and their henchmen. Octavian pursues Livia as an "appropriate" bride, and issues Mark Antony an ultimatum he knows he can't refuse.
The people of Rome are starving. There have been many grain shortages over the past few months, but things have gotten particularly bad. In hopes of keeping the people from openly rebelling, Octavian sends Atia and Octavia to Alexandria in order to negotiate a deal with Mark Antony, though his real reasons for their trip is soon revealed. Meanwhile, Titus Pullo and Lucius Vorenus must try to keep the peace amongst many of the mercenaries who are in Rome.
Following his naval defeat at Actium, Marc Antony returns to Egypt, where he and Cleopatra settle into a world of debauchery. Octavian tries to use Pullo as leverage to Vorenus to gain acess to the palace, but Vorenus stays loyal to Antony. Finally, it is Cleopatra who dupes Antony, saving her own life by sacrificing her honor. Ceasar Augustus triumphs in Rome.