Sydney discovers a link to her missing two years in the form of Simon Walker, the dangerous and sexy leader of a group determined on retrieving deadly biological weapons. Meanwhile, Vaughn struggles with his own feelings of jealousy and longing while Sydney is on her mission, aware of the pressures his job is putting on his marriage to Lauren. Jack takes matters into his own hands to protect his daughter, purposefully revealing Sydney's deadly secret to Dixon in order to preserve her position inside the CIA.

Sydney and Vaughn are sent to retrieve the Doleac Agenda to gain an advantage over The Covenant. For this, Sydney and Weiss must convince rogue security systems designer Toni Cummings to help the CIA break into a Lethal Response System. Meanwhile, Sark approaches an unlikely ally to kill the Covenant's Cell leaders.

Sydney and Jack warn a disbelieving Vaughn about their suspicions of Lauren being the CIA mole. Meanwhile, Bomani and Sark take possession of the Rambaldi machine, Sydney and Vaughn must stop a Covenant virus that's crippling medical facilities around the world, Sloane's secret is revealed to Jack, and Bomani begins to lose faith in Lauren's ability to carry out her Covenant missions.

While Sydney and Nadia argue about Nadia's acceptance of Sloane's fatherly concerns, Sloane worries about Nadia's well-being when she and Sydney go undercover as wealthy, irresponsible young heiresses to uncover the whereabouts of a deadly chemical.

Dixon enlists Sydney to help him prove that Sloane is double-crossing the CIA and using APO to steal the Blackwell Index, a master blackmail list, and to reconstruct the Alliance. Sydney makes her way into Sloane's house so as to copy the encryption key from his secure phone and crack his calls. When Nadia finds her, she becomes disappointed in her sister. Meanwhile, Vaughn discovers something disturbing about his father when he visits his comatose uncle.

Sydney must protect the life of a civilian, whom she unintentionally put in danger. Meanwhile, Jack plans a visit with an old friend, and Vaughn uncovers more disturbing secrets about his father.

Rambaldi's catastrophic endgame begins to fall into place as a giant version of the Circumference/Mueller device is found floating over city in Russia, driving the citizens made. After a wounded Dixon reveals that Irina is alive, Sydney, Nadia, and Jack set off to find her. Irina had been captured, and then duplicated using Project Helix, in order to give the impression that she was dead.

Sydney and Nadia discover Irina is being held inside a camp in Tikal, safely in the clutches of Elena's army. Irina had apparently been working to counter Elena's organization, the Covenant, and actually PREVENT the Rambaldi endgame. Irina tells of a page she destroyed, a page that was key to Rambaldi's endgame. Under torture, she finally broke and recreated it for Elena. After a short respite, the transport turns towards Russia, and Sydney, Vaughn, Jack, Nadia, and Irina parachute down, towards Elena, Sloane, the Circumference....and destiny.

After learning that the man she has known as Michael Vaughn is under investigation and suspected of being a double agent, Sydney begins to question whether their business and personal relationship over the years had all been a lie.

Rachel and Sydney have to join forces with Julian Sark to prevent a deadly micropulse bomb from falling in the hands of a dangerous mercenary.

While the gang starts to learn more about the Prophet 5, Sloane is distressed to learn that Prophet Five's cure for Nadia is just as likely to kill her. Meanwhile, Devlin returns, the search for Anna Espinosa continues, Rambaldi's prophetic Page 47 resurfaces, and Sydney offers Renée a job at APO.

In the first part of [the] Alias two-hour finale event, 'Reprisal,' Sloane takes Marshall and Rachel hostage in order to discover a crucial clue to Rambaldi's ultimate endgame, as Sydney, Vaughn and APO race to stop him.