The "Jake Story" is one part of Resident Evil 6's campaign storyline, based around the characters Jake Muller and Sherry Birkin. The principle plot to this campaign is Carla Radames' plan to modify the C-Virus by taking Jake's blood sample.
Though young, Jake Muller is a seasoned mercenary, grinding out a living fighting for the rebels in Edonia. Life in the eastern European state suddenly changes with the arrival of a strange medicine, billed as nutritional supplements. Surprisingly, all who take the supplements begin to change; losing all human rational, they transform into monsters. Jake alone is left unaffected.
Already confused by the chaos erupting at the base, the sudden appearance of U.S. agent Sherry Birkin only further confounds the young mercenary. Sherry explains that the so-called "supplement" is, in fact, the C-Virus: a horrible new mutation-inducing virus developed by the terrorist group Neo-Umbrella.
Jake however, as Sherry explains, apparently carries antibodies; this fact quite possibly makes him the last and only hope for humanity in fighting the virus, and is the reason Sherry needs his assistance. True to his mercenary nature, however, Jake insists that if he really is the key to saving the world, his help will come at a cost; an agreement of fifty million dollars for his services is met, and the two go to make their escape from the embattled camp.
At that same moment, Neo-Umbrella unleashes a monstrous hunter, known as Ustanak, to pursue the two.
Amidst the ensuing deadly game of cat-and-mouse, the pair run into Chris Redfield of the BSAA—Chris being the older brother of Claire, to whom Sherry owes her life. With Chris' help, the two manage to escape the scene via a BSAA helicopter. However, Ustanak's relentless pursuit continues. In the creature's attempt to capture Jake, the helicopter sustains massive damage and begins to crash. Sherry and Jake manage to bail out, however, as they near the ground, a piece of the helicopter tears through their parachute, causing them to fall.
Jake and a mortally wounded Sherry lie on the snow-covered mountainside. Sherry had shielded Jake from a large fragment of the destroyed helicopter, which is now lodged in her torso.
Jake removes the massive steel hunk from her expecting the worst, yet to his astonishment, her wounds heal right before his eyes.
Stranded, the pair seeks refuge from the elements in an empty cottage. Safe inside, Sherry proceeds to tell Jake about the 1998 Raccoon City incident where her father had injected her with a new kind of virus—the source of her remarkable healing ability.
The two realize they share a bond, as each of them carries a unique burden, setting them apart from normal people, and it brings the two of them closer together.
The tranquil of this interlude is soon broken by an attack from Neo-Umbrella.
Shaking off an assault by J'avo and running from the ever-persistent Ustanak, Jake and Sherry somehow manage to make their way through the frozen landscape and reach the Edonian border. Here, too, they are surrounded by Neo-Umbrella and captured. The mysterious woman that had distributed the C-Virus to Jake's mercenary group, suddenly appears before their eyes. She tells Jake about Albert Wesker, a man who had nearly destroyed the world and, according to her, is also Jake's father.
Following the chase through the snow-covered mountains of Edonia, Jake and Sherry are abducted by Neo-Umbrella and taken to a facility in China. Here, they are subjected to test after test, day in and day out, for a grueling six months. One day Jake finds an opportunity to break free, and after eluding his captors manages to shut down the facility's power before making a run for it. Noticing the power-outage, Sherry also seizes upon this opportunity to escape from her room. After some commotion, the two are finally reunited; however, in contrast to Sherry's joy, Jake is brooding, harboring anger over thoughts of his father, Albert Wesker. Jake feels cheated by life, having been cursed with his father's blood.
Sherry admonishes Jake's sulking, arguing that how he lives is not up to his father's legacy, but up to him. To this, Jake has no reply.
Making contact with the U.S. government, the pair discover that Sherry's superiors are also in China and quickly make plans to rendezvous.
Breaking through wave after wave of J'avo, Jake and Sherry find a motorcycle and make a daring escape from the facility.
Desperately making their escape through the heart of the bioterror attack in China, Jake and Sherry are eventually surrounded by Neo-Umbrella's forces. Just when things are looking bleak, Chris and the BSAA show up and rescue the pair. However, under strict orders to avoid contact with others, Sherry and Jake part ways with Chris without so much as a word.
On the run once more, Sherry and Jake witness a U.S. government plane crash right before their eyes. When they arrive at the site of the crash, they find Leon Kennedy, who—years ago—had saved Sherry's life.
Leon informs Sherry that Derek Simmons, her superior, is in fact the man behind the bioterror outbreak. Having made plans to rendezvous with Simmons but now unsure of if she can trust him, Sherry tells Leon where Simmons is and agrees to meet with Leon again at her rendezvous point.
After arriving there, Sherry finds Leon and Helena facing off against Simmons. Simmons readily admits that he indeed is behind the outbreak, but claims that it was in order to maintain both U.S. and global stability. Simmons then orders his guards to shoot Leon and Helena. Having a personal score to settle with Simmons, Leon and Helena urge Sherry and Jake to escape, offering them cover.
However, Sherry and Jake run right into a nest of J'avo and are quickly overpowered. Despite their best efforts, the pair are caught once more.
Jake and Sherry find themselves trapped in Neo-Umbrella's undersea facility at the bottom of the ocean.
The situation seems hopeless until Chris and Piers, following a tip from Leon, show up to rescue them.
However, when Chris admits that he killed Jake's father, Wesker, Jake loses himself to emotion and reflexively pulls his gun on Chris. The situation is tense. Just then, Neo-Umbrella's massive B.O.W., Haos—a creature capable of bringing ruin upon the entire planet—awakens from its cocoon.
Understanding how valuable Jake's blood is to the world, Chris tells Sherry and Jake to make their escape while he and Piers fight Haos.
Jake and Sherry do not get far before they again run into Ustanak, and are forced into a brutal fight.
The seemingly unstoppable hunter refuses to be defeated even after having its body burned away by fiery magma—its pursuit unforgiving to the end.
Finally, Jake and Sherry manage to defeat the creature and make their escape from the facility.
Following their adventure together, Jake hands over a sample of his blood to Sherry and disappears—though not before lowering his original asking price of fifty million dollars to just fifty. From Jake's blood, a vaccine for the C-Virus is distilled, and the outbreak is gradually contained.