Agent Jack Bauer, having been taken prisoner by China 20 months earlier, is released under a deal arranged by President Wayne Palmer. Jack is immediately asked to sacrifice himself to Abu Fayed, who has offered CTU Hamri Al-Assad, who is believed to be the terrorist mastermind behind the suicide bombings of the last 11 weeks. Jack finds out, however, that Assad is actually trying to stop the attacks, which were orchestrated by Fayed. He escapes and saves Assad which requires him to kill Curtis Manning who is bent on revenge. Having found out that Fayed is planning to detonate five suitcase nuclear bombs, CTU agents attempt to retrieve one of them but they are too late. While crying over the loss of his friend, Jack watches in horror as a nuclear blast destroys Valencia.
Jack discovers that his father Phillip and brother Graem are working against CTU and have been for some time. This reunites Jack with his nephew Josh Bauer and sister-in-law Marilyn Bauer who tells him that Audrey Raines is dead. Morris O'Brian is lured out of CTU, captured by Fayed and forced to arm the remaining nuclear bombs. After defusing one of them, Jack enlists the help of former President Charles Logan. Logan claims that his connection with the Russian Consulate General, Anatoly Markov can help Jack find Dmitri Gredenko, a general planning to arm RQ-2 Aerial Drones with the bombs to attack the U.S. Dissatisfied with Wayne Palmer's leadership during the crisis, Reed Pollock and a co-conspirator named Carson plan to assassinate Palmer and frame Al-Assad for it. Before Tom Lennox can prevent the attack, their bomb explodes, killing Assad and leaving Palmer in critical condition.
Vice President Noah Daniels assumes executive powers and threatens retaliation. Logan fails to blackmail Markov into giving up Gredenko, so Jack breaks into the Russian Consulate and tortures information out of him. President Logan convinces his ex-wife Martha to call the Russian First Lady, Anya Suvarov. As a result, Yuri Suvarov authorizes action against the consulate by a CTU team (led by new Director of Field Operations Mike Doyle). Jack immediately gives CTU Gredenko's location, but it is too late, as Gredenko has already launched a drone toward San Francisco. Jack manages to locate the drone's pilot and crash land the drone but radiation is released during the crash. Noah Daniels authorizes a nuclear strike against the Middle-East but Wayne Palmer is brought out of his coma to intervene.