The game features past games' stories through a first-person perspective and does not allow free movement. It features Resident Evil Zero, Resident Evil, and Resident Evil 3: Nemesis to show the events that lead to Umbrella's end in 3 scenarios with sub-stories that were never seen before explaining other events. It retcons several events through the series and is narrated by Albert Wesker.
There is also a final scenario unlocked after beating the past three called "Umbrella's End". It features an original story set in a Russian Umbrella facility in February 2003. As the name implies, it ends Umbrella once and for all.
The game also features a whole new character named Sergei Vladimir, an Umbrella officer and head of the UBCS, who hails from Russia. He serves as the game's main antagonist. He has a crucial role in the last scenario and has several appearances through the aforementioned sub-stories.
The game follows the story behind the downfall of the Umbrella Corporation by revisiting scenarios from Resident Evil Zero, Resident Evil, and Resident Evil 3: Nemesis. It concludes with an assault upon an Umbrella stronghold maintained by Sergei Vladimir. In total, there are four main chapters with ten additional playable scenarios, divided up into a total of twenty two levels. You should note that Train Derailment, Mansion Incident and Raccoon's Destruction (with the exception of the sub-stories) are uncanon and are a quick recap of RE0, RE and RE3:Nemesis
All scenarios in this chapter take place during the events of Resident Evil Zero.
Train Derailment: A summation of Resident Evil Zero, divided up into three acts where the player chooses between Rebecca Chambers or Billy Coen. The first act follows Rebecca and Billy through the train and ends with a boss battle with the Stinger. The second takes place in the Umbrella Executive Training Center and the church and a boss battle with the Infected Bat. The last scenario takes place in bowels of the Arklay Treatment Plant and the battle with the Queen Leech.
Beginnings: Reveals Wesker's actions during this timeframe. The t-Virus escaped in Umbrella's Training Facility due to Dr. Marcus' attack and Wesker must escape from the facility in order to pursue his next mission, luring the S.T.A.R.S. team to the Arklay Laboratory. The Proto Tyrant (T-001 Model)'s death is retconned as being at the hands of Wesker. After successfully reaching the surface, Sergei Vladimir confronts him and, not noticing Wesker's betrayal and unknowingly mistaking his actions as failure, dispatches a derivation of the Tyrant (T-103 Model)s called Ivan to punish him. Wesker barely manages to escape with his life.
Mansion Incident: A summarization of Resident Evil, divided into three acts where the player can choose between Chris Redfield and Jill Valentine. It first follows them through their meeting with the Spencer Mansion, ending with a battle with the Yawn and Rebecca's level. It continues through the gardens and outer areas, ending with a battle with the Plant 42. Finally, through the labs and a battle with the Tyrant (T-002 Model).
Rebirth: Wesker awakes in basement level four of the Arklay Laboratory, resurrected by a special virus sample he received from William Birkin and discovers that the Tyrant has been destroyed and the mansion's self-destruct system has been activated. He attempts to get Umbrella's data, but realizes that it has been backed up to a supercomputer called U.M.F.-013 by Sergei Vladimir. Furthermore, his access privileges to the mainframe system have been revoked by the Red Queen. With minutes to spare, Wesker changes his plans and fights his way out of the mansion. At the very end, he finds the exit blocked by his long lasting test subject, the nearly immortal Lisa Trevor, whom he decides to give the final treatment.
All scenarios in this chapter take place during the events of Resident Evil 3: Nemesis.
Raccoon's Destruction: A summation of Resident Evil 3: Nemesis, divided up into three levels where the player can choose between Jill Valentine or Carlos Oliveira.
Part 1: This segment follows Jill and Carlos' way to the Train Station. . The boss is the Grave Digger.
Part 2: This segment follows Jill and Carlos going through a train station to the R.P.D. At the end of this segment, the player/s must combat over 20 Hunter Rs'.
Part 3: This final segment follows Jill and Carlos' exploration through the R.P.D., and their fight with the Nemesis.
Death's Door: Covers Ada Wong's mission to bring the G-virus sample back to Wesker. Although heavily injured during the events of Resident Evil 2, Ada survived and returned to the surface. She attempts to rendezvous with a contact at the Apple Inn, but finds him already dead, having killed himself. Wesker then contacts her via phone and informs her that she has failed, and that her betraying them and rescuing Leon S. Kennedy would have consequences for their organization. Ada shows Wesker a tissue fragment of Birkin's dead body serving as a sample of the G-Virus, at which point he tells her that Raccoon City is about to be bombed and a helicopter with an Umbrella officer is the only possible way to leave the town, thus saving her life with the information. Ada handily defeats a Tyrant R that was absorbed by Nyx. After the fight, she uses the hook shot she collected from the dead contact to board the chopper. Inside the helicopter, Sergei Vladimir and an unnamed Umbrella executive talk about stealing the computer core, U.M.F.-013, from his own company.
Fourth Survivor: A retelling of the bonus scenario of the same name introduced in Resident Evil 2. It covers special agent HUNK's mission to return the G-virus sample to Umbrella. In this remake, radio interference causes the player to pick up a variety of transmissions, such as the police's doomed attempts to fight the zombies, the last broadcast of a surrounded radio station, advertisements for various Umbrella products, the dying pleas of HUNK's only surviving teammate, and someone screaming "Raccoon City! Raccoon City!". HUNK makes it to the roof of the police department and is picked up by a rescue chopper.
All scenarios in this chapter are brand-new and have never been portrayed in the series before. They take place in the year 2003, five years after the destruction of Raccoon City, and one year before the events of Resident Evil 4.
Umbrella's End: A three-part story dealing with Chris Redfield and Jill Valentine attacking and securing Umbrella's most important remaining facility, the Russian stronghold in the Caucasus region, where the Red Queen supercomputer and all of Umbrella's data is being held. Anticipating an attack, Sergei Vladimir unleashed the t-Virus in his own facility, along with the most powerful B.O.W.s the company had to offer. Jill and Chris penetrate deep into the facility, ultimately destroying Umbrella's most sophisticated bio-weapon ever, the T-A.L.O.S. project.
Dark Legacy: As Chris and Jill unintentionally cause a diversion, Albert Wesker also infiltrates Sergei's stronghold with a much more insidious mission. Sergei soon confronts Wesker, and sends two of his Tyrants to kill him. Wesker proves to be more than a match for the Ivan, thanks to his superhuman abilities, and continues his infiltration of the facility. In the end, Wesker faces Sergei for the last time, who self-destructs himself with the t-Virus and mutates him into a monster. Wesker kills him and steals all the data Umbrella accumulated over years of research, and then wipes the computer clean. By gaining the data, Wesker starts his plan to revive the Umbrella Corporation under his command, as revealed in Resident Evil 4 to be his main objective.
During and after the credits, more about the storyline is revealed. It is stated that the Umbrella Corporation was finally found guilty on all charges of its involvement in the Raccoon City outbreak, though the prosecution remained quiet about how they acquired the necessary information. As a key witness, an anonymous witness (Wesker) close to the suspect also implicated Oswell E. Spencer personally, starting a global manhunt for the Umbrella founder. At the very end of the game, Wesker is shown entering the same command room that he uses in Resident Evil 4. He places all of the stolen Umbrella data into his computer, allowing him to take possession of all the company's assets and information, and promises that he will meet Spencer again and usher in a new era for himself.