Set in 2005, between the events of Resident Evil 4 and Resident Evil 5, Revelations depicts the Bioterrorism Security Assessment Alliance (BSAA), a counter-terrorism group which Chris and Jill have co-founded, shortly after its establishment. The game begins as the latter and her partner, Parker Luciani, board the Queen Zenobia.
Set mainly in Europe, Revelations sees the player characters through ravaged cities, ports, and snowy mountains. Jill and Parker are sent out by BSAA head Clive R. O'Brian to search for Chris and his new partner, Jessica Sherawat, who have reportedly gone missing during a mission. Meanwhile, Chris and Jessica are operating in a snowy mountain region, searching for evidence of the return of Il Veltro, a bio-terrorist organization responsible for the attack and subsequent outbreak in Terragrigia, an artificial aquapolis that was utterly destroyed on orders from Morgan Lansdale, director of the Federal Bioterrorism Commission.
Jill and Parker find their way into the Mediterranean Sea, acting on Chris' last known coordinates. They find themselves taking a tugboat to a seemingly abandoned cruise ship known as the Queen Zenobia. On board, they find horrific mutants known as Ooze, victims of the t-Abyss virus, and are unable to locate Chris or Jessica. Instead, they find a dummy of Chris and are knocked unconscious by an Il Veltro agent, stripped of their weapons, and separated.
Chris and Jessica, meanwhile, find a base of operations for Il Veltro; an airstrip in the mountains. Being informed by O'Brian that Jill and Parker are missing in the Mediterranean, they are then sent out to investigate their whereabouts. Meanwhile, the pair of Keith Lumley and Quint Cetcham are dispatched to the airstrip to find out more about Il Veltro's actions. Back on the Queen Zenobia Jill wakes up in one of the cabins and is contacted by Parker who says he woke up on the other side of the ship and to regroup on the bridge. After meeting up they are attacked by an FBC agent named Raymond Vester who knows Parker from when he was an FBC agent. Meanwhile, at the airstrip Quint and Keith find video footage of an invisible creature killing a Veltro operative. Which is later revealed to be a new form of Hunter which has been infected with the t-Abyss which allows it to turn invisible for sneak attacks. Meanwhile, Chris and Jessica land on a ship thinking its the Queen Zenobia but discover that they are on the Queen Zenobia's twin the Queen Semiramis. On the Zenobia Jill and Parker are desperately trying to escape the flooding engine room which after they escape they head to the Comm tower to try and contact O'Brian to report whats really going on. But are met with bad news that the Regia Solis, the satellite used to fry Terragrigia using the sun's power, has been reactivated and is being aimed at the Queen Zenobia. Luckily, Quint leads Jill and Parker (via comm link) to the UAV (one of the three used in the Terragrigia attacks to spread the virus) on the ship's bow, and the two race against time to find the controls. with the controls, Jill and Parker use the UAV's chaff to guide the Satellite's targeting system away from the ship. However, as the Regia Solis hits the UAV, a wave hits the ship, and threatens to sink the Queen Zenobia.
Meanwhile, Quint and Keith discover that O'Brian had orchestrated Veltro's re-emergence along with other crucial information. However, they lose contact with O'Brian when an airstrike decimates Valkoinen Mökki. Chris and Jessica arrive to the Queen Zenobia. At the same time, Jill and Parker are confronted by the Veltro operative, who poses various questions hinting at a larger conspiracy. However, before he can reveal anymore, Jessica shoots him. Parker unmasks him to discover it was Raymond. He seemingly dies after whispering something to him. Afterwards, Chris and Jill make their way to the ship's laboratory to stop the virus from contaminating the sea, while Parker and Jessica search for a way to stop the ship from sinking. During the search, Parker turns his gun on Jessica, suspecting her of being an FBC mole, as told by Vester. At the same time, Raymond reveals himself to be alive, having worn a Kevlar vest, and working with O'Brian. Jessica wounds Parker and initiates the self-destruct sequence, confirming her to be the mole. Having found the laboratory, Chris and Jill are confronted by Lansdale, via video uplink, revealing that he worked with Veltro in the Terragrigia Panic in an effort to increase the FBC's funding and international influence; notes left by former crew members reveal that he had dispatched a research team to create a vaccine, and then killed them off by releasing the ship's monsters after they'd sent it to him. Despite the Queen Zenobia self-destructing, they manage to neutralize the virus. Pilot Kirk Mathison contacts Chris and Jill informing them that he is there to extract them. They then meet with an injured Parker but despite the pair's attempt at saving him, Parker falls into the fire below a broken catwalk.
O'Brian informs Chris and Jill about the truth behind the mission: he had orchestrated the events in an effort to gather evidence of Lansdale's involvement in Terragrigia. He then informs them of the results from Keith and Quint's data analysis: the existence of a third sister ship known as the Queen Dido below the ruins of Terragrigia, which was destroyed by Lansdale to eliminate incriminating evidence of his involvement. However, Lansdale then proceeds to arrest O'Brian, cutting off communications. Jill and Chris search for Jack Norman, the leader of Veltro, knowing that he holds evidence against Lansdale. However, he has gone delusional, and survived a year by injecting himself with T-Abyss and resisting mutation through his own desire for vengeance; he then injects himself with an overdose of the virus, believing Chris and Jill to be FBC sent to kill him, and transforms into a new type of Tyrant known as the "Final Form Abyss". After a long battle, he is finally killed, expressing his relief that he could finally be at peace. Chris and Jill then broadcast the video via Norman's PDA, exposing Lansdale. O'Brian is immediately released and arrests Lansdale. The truth behind Terragrigia went public and the FBC was dissolved. Parker, who was saved by Raymond from the explosion, was found adrift off the shore of Malta and, after a month of recovery, resumed his position as a Special Operations Agent for the BSAA; while O'Brian decides to take responsibility for his actions in orchestrating the entire mission and steps down as director of the BSAA. Quint and Keith are revealed to have survived the air raid. The game then shows Chris and Jill walking up to the Spencer estate from the "Lost in Nightmares" episode of Resident Evil 5. In a post-credits scene, Raymond approaches Jessica at a cafe and gives her a sample of T-Abyss Virus. She asks him why he saved Parker, with him replying that he "had his reasons", whilst removing his sunglasses.