Synopsis:

The game begins as Chris Redfield is deployed to Kijuju, Africa, to join Sheva Alomar in the apprehension of Ricardo Irving, who is attempting to sell a bio-organic weapon on the black market. Along the way, they witness a local being fed a parasite, which quickly takes control of his body, turning him into a Majini. As they progress, almost all Kijuju locals seen by Chris and Sheva have been turned into Majini. While moving to the location of Irving's deal, Chris and Sheva find Alpha team dead, except Captain DeChant, who gives them a hard drive containing data about Irving before he dies. Shortly after, a friendly helicopter is downed, and all nearby BSAA units are ordered to go to the crash site. At the crash site, Chris and Sheva are ambushed by Majini on motorcycles, but are then saved by Delta team. Among Delta team is Josh Stone, Sheva's mentor who gives Chris data from a hard drive that contains a picture of Jill Valentine, his old partner, who was presumed dead after a confrontation with Albert Wesker. Chris does not tell Sheva about the image and they continue. They eventually confront Irving and during this confrontation, a hooded figure arrives to aid Irving's escape. Irving leaves behind files which indicate that an oil field in the Marshlands, which was used to test out bio-organic weapons, is the deal location. The previously suspected location is discovered to be a hoax to slow the BSAA while the actual deal was taking place. Chris and Sheva report this to headquarters and then attempt to regroup with Delta team. Upon arriving at the rendezvous point, they find that Delta team has also been killed by a bio-organic weapon, but Sheva cannot find Josh among them. After defeating the bio-weapon, Sheva suggests reporting back to HQ, being that they are the two sole survivors. Chris refuses, admitting to Sheva his true reason for participating in the mission, and expresses his determination in finding out if Jill is still alive. After a brief argument, Sheva concludes that they are partners, and she will help him all the way. They continue on to the Marshlands, eventually finding Josh alive. They pursue Irving on a boat, but he escapes again and the oil field is blown up while the two escape on a speedboat with Josh. The trio locate and catch up to Irving's boat, and Chris and Sheva board it. Irving confronts the duo, and then injects himself with a virus, which causes him to mutate into a gigantic beast. Chris and Sheva defeat the mutated Irving, who is detached from the gigantic beast body, and upon death, he tells Chris that he will find answers to his questions in a nearby cave.

Upon arriving in the cave, Josh leaves the pair in order to report to HQ. The cavern leads Chris and Sheva to the underground kingdom of the Ndipaya tribe. As they explore, they find an underground base, one of the first to be set up by Umbrella, but currently operated by Tricell. Chris and Sheva find evidence and documentation that the Progenitor virus, which is the component in both the T and G-virus that controls a subject's body, was found and manufactured here. The Progenitor virus was manufactured from a plant residing in the Ndipaya kingdom, called the Stairway to the Sun. The plant was used in Ndipayan ceremonies, but Ozwell Spencer took interest in it, and drove the Ndipaya out to build a base and study the plant, which eventually yielded the Progenitor virus. Chris and Sheva progress through the underground laboratory, and find a massive chamber with thousands of capsules containing human test subjects. The facility is documented in one of the hard drives, so Chris searches the computer database for an entry about Jill. The elevator takes them to the capsule in which Jill was being held. The bio-organic weapon, U-8, attempts to stop them from going up, but Chris and Sheva defeat the weapon and continue. They reach the capsule and open it to find it empty. Excella Gionne then appears on a computer screen and warns them to leave. Chris and Sheva later intercept a radio transmission of Excella talking to Wesker, indicating Wesker's survival. They confront Excella, but she infects a test subject with the Uroboros virus, which turns him into a bio-weapon. After killing the weapon, the two pursue Excella, eventually catching up to her. When interrogating Excella, Chris and Sheva are attacked by the hooded figure who aided Irving's escape. Wesker then reveals himself and unmasks the hooded figure, Jill, who is hostile and fights alongside Wesker. After a short fight, Wesker escapes leaving Chris and Sheva to battle Jill. They spot a device on Jill's chest, which they remove, and she regains control of her body. She apologizes for her actions and urges

Chris and Sheva to pursue Wesker. Chris, who is reluctant to leave Jill, grudgingly agrees. Chris and Sheva emerge on the surface and spot Wesker and Excella boarding a cargo ship. They pursue them and board the ship. They find Excella but she escapes, dropping a case of full syringes, which Sheva collects. Meanwhile, Wesker reminisces about a confrontation with Spencer, who tells Wesker that he is the only surviving subject from the "Wesker Plan," which was an attempt to create the ideal human being for Spencer's envisioned utopia. Spencer fantasizes about being the god of this utopia and Wesker impales him, declaring, "The right to be a god? That right is now mine."