On July 23rd, 1998, the residents of Raccoon City are wary and upset due to a series of bizarre murders that have been taking place in the forests of the nearby Arklay Mountains, a once-popular hiking and camping site.
But this is of little concern to a team of Umbrella workers currently speeding through those same forests aboard the private train, the "Ecliptic Express". Their attention is focused on their orders from the company; to reopen a discarded training facility and research lab that had been abandoned over a decade ago. Alas, they are soon proven wrong in their nonchalance when their train is suddenly assailed by an enormous swarm of mutant leeches, who force their way into the cabins and kill every passenger and staff member aboard, bringing the train to a screeching halt.
Two hours later, STARS Bravo team —Enrico Marini, Richard Aiken, Kenneth Sullivan, Ed Dewey, Forest Speyer, and, on her first mission, new recruit Rebecca Chambers— flies over the area by helicopter. They're in the middle of their investigation into the spate of murders, hoping to find what has been terrorizing the good people of Raccoon City.
Forced into landing by a sudden engine failure, the group spreads out to begin investigating their surroundings. They discover a crashed military transport vessel, its military police drivers dead at the scene. Searching through it, they learn that the vehicle was carrying a war criminal — disgraced Lieutenant Billy Coen — to be executed at the nearby Regarthon Base. He, however, seems to have survived the crash and fled. Considering this a secondary mission, Bravo Team splits up to survey the immediate area.
As she explores, Rebecca finds the Ecliptic Express, and boards it. To her horror, she finds its seats cars full of dead bodies... several of which then animate and attack her! Gunning them down, she tries to make her way to the engine itself, but is unable to progress due to a locked door. As she retrieves a key to the dining car from a nearby corpse, she is confronted by Billy Coen, who holds a gun on her from behind. After realizing she's just a rookie - and a medic - from STARS, Billy decides she's not a threat and proceeds to leave, despite Rebecca's rather feeble attempts to assert herself.
Before Rebecca can give chase, her teammate Edward Dewey suddenly bursts in through the window. Though she rushes to his aid, he is mortally wounded from vicious animal bites. With his dying breath, he warns Rebecca that the forest is full of "zombies and monsters". She doesn't have long to ponder this before Edward's killers - a pair of zombie dobermans - come charging through the window in turn.
Killing them, the shaken Rebecca tries to give chase to Billy. In the passenger car, Captain Enrico contacts her by radio. The transmission is awful and cuts off shortly, but he manages to warn her that Billy Coen is responsible for the deaths of 23 people and was recently institutionalized. His last words before transmission ceases are to warn her that Coen wouldn't think twice of killing her.
And yet, he doesn't seem in the slightest interested in that. Catching up to her as she enters the dining car, Billy actually proposes that he and Rebecca team up. When she incredulously points out that he's a wanted felon, he retorts that there are bigger things to worry about at the moment. Unable to convince her, he then tells her to go on ahead and see how well she does. As the power has been cut, sealing the automated doors to the kitchen shut, Rebecca heads upstairs to the dining room.
Here, she finds an old man seated at a table, one who seems to be a survivor... until he turns to look at her and his head falls off of his shoulders! As Rebecca screams in horror, the corpse splits apart and reveals itself to be a swarm of mutated leeches, which quickly reassembles itself into a grotesque parody of the man she just saw. After a brief facedown, the "leech zombie" reverts to its swarm form, which rapidly skitters across the floor and engulfs her.
Before it can hurt her, Billy comes to her rescue, scaring off the leeches with some well-aimed shots. As he helps her to her feet, the two of them see the swarm regrouping at the feet of a strange young man in a white robe, watching the train from a nearby hill. At that point, the train starts moving again, and Rebecca reluctantly agrees to team up with Billy - things are just too dangerous to go it alone.
Since they have nowhere else to go, one of the duo climbs up onto the roof of the dining car and restores power by fixing a sundered cable. However, they are attacked by a sudden flurry of leeches, and fall into the serving room part of the dining car's upper floor. This would normally be a minor inconvenience, but something is jammed in the lock, leaving them stuck and forcing their partner to go it alone to find some way to get them out.
Fortunately, there's a dumbwaiter nearby that links the serving room to the kitchen - more usefully, there's a key to the conductor's room, which they send down via the dumbwaiter. The free member of the team retrieves the key and returns to the passenger's car. A brief trip to the second level proves fruitless; the hallway near the stairs is blocked off by a huge mass of mutant leech eggs. So, they continue on to the conductor's room. Here, they find a briefcase with a lock that needs two ring-shaped keys, and a ladder leading to the second floor of that car. Exploring this upper deck, they find a hunting gun (a double-barrel shotgun) and an icepick... the former of which comes in handy, as they are attacked by the Stinger; a scorpion-based B.O.W the train was transporting to its destination.
Returning to the kitchen, the ice pick is sent up to the server room and frees the trapped member of the duo. Reunited, Rebecca and Billy make their way to the back-most car, where they discover a hookshot and one of the rings needed to unlock the conductor's briefcase. Returning to the passenger car, Rebecca uses the hookshot to rappel to the roof through a nearby open window, where a convenient hole allows her to access a room that had been blocked off by the mass of leech eggs. Here, she retrieves the second ring and, as the leeches choose that moment to conveniently hatch, she is able to rejoin Billy and open the conductor's briefcase, revealing the keycard needed to access the engine.
As they unlock the door, they overhear a brief radio conversation between two gas-masked, armored soldiers to unknown superiors. Calling themselves "Delta Team", they claim to have secured the train, but as they listen to their superiors' orders, they are attacked by a swarm of leeches and killed.
Unbeknownst to Rebecca, Delta Team was working for none other than Albert Wesker and Wiliam Birkin, and were investigating the mysterious contamination of first the Arklay research lab, and now the Ecliptic Express and the training facility. They had ordered the train's destruction, but the leeches had put paid to that.
Having been unable to save the strangers, Rebecca and Billy step past them and enter the engine room. By this point, the train is picking up speed, and will derail or crash; one of them has to race back to the end car so they can throw the emergency brakes. Despite the swarm of zombies in their way, including the now-reanimated Edward Dewey, they fight their way there just in time and manage to apply the brakes... barely.
The train comes to a catastrophic halt in a hidden, underground station, but miraculously the two survive. Picking off the zombies that were thrown clear of the burning wreckage, they use a nearby door that leads them through a short set of sewer tunnels and up a ladder into the main hall of a mansion. Though weakly lit by both oil lamps and lightbulbs, the dust makes it evident that nobody's been here for a long while.
A centerpiece in the floor consists of an enormous copy of the Umbrella Corporation's logo, and the words "Umbrella Research Center". On the small platform midway up the main staircase to the second floor, they find a faded oil portrait of an old man - one "First General Manager James Marcus", whom Rebecca recognizes as the man that the leech monster on the train briefly assumed the form of.
As they study it, they are being watched by Wesker and Birkin. Both men are as surprised as the trapped partners when an ancient public address system suddenly broadcasts James Marcus' recitation of the Umbrella motto: Obedience breeds Discipline; Discipline breeds Unity; Unity breeds Power; Power is Life. To their surprise, their signal is suddenly hijacked by the strange young man that Rebecca and Billy saw in the forest, who claims responsibility for both T-virus outbreaks. His motivation? Revenge on Umbrella for the assassination of James Marcus, which he emphasizes by summoning leeches together and making them assume the form of the elderly Marcus.
Unaware of this, Rebecca and Billy begin exploring the mansion. It's not easy, as it the remnants of the former clean-up crew, now zombies, still prowl the dusty halls, and many rooms have been sealed off behind ancient puzzle-locks. Undaunted, they set to figuring out what was going on, stumbling across assorted documents that hint at the inhuman experiments that were conducted here. Despite a run-in with a giant centipede in the attic, the two partners collect various keys and unlock the doors, ultimately assembling two stone busts; a black bust of a male demon emblazoned "Statue of Evil" and a white bust of a female angel emblazoned "Statue of Good".
When these are placed on the scales of a statue on the second floor of the main hall, the portrait of James Marcus slides aside to reveal a hidden set of sub-levels. Descending, they find a medieval style dungeon, with dried gore suggesting it was used at some point. Billy gives Rebecca a boost into a neighboring cell, where she manages to reactivate the mansion's power supply. However, this captures the notice of the strange young man, who, in response to Rebecca's "trespassing", unleashes a mutated ape B.O.W, the Eliminator, on her.
Ambushed by the feral creature, Rebecca narrowly evades death at its claws and fangs, only to be betrayed by the floor giving weigh under her. Billy races to her aid, fighting his way through the other monsters in the sub-levels and rescuing Rebecca before she can fall through a hole into an underground river.
Whilst this is happening, Birkin and Wesker discuss the stranger; if he can reveal the truth behind Marcus' assassination, it will mean the end of the careers of both men, as well as Lord Spencer's. Wesker is indifferent; as he reveals to Birkin, he had already planned to leave Umbrella, and will abandon the company after he completes his plan to lure STARS Alpha Team to the Arklay lab to acquire more test data. Birkin refuses to join him; he has yet to finish his work into refining the G-Virus, which will be more powerful than the T-Virus. So, he determines to find and activate the self-destruct system for the research center, which he hopes will take care of the problem once and for all.
Back in the dungeon, Rebecca is contacted by Captain Enrico Marini, who asks if she's found Coen. Grateful for his repeatedly saving her life, she lies and claims she hasn't. Once he's gone, she asks Billy at least tell her the truth about his conviction. Reluctantly, Billy explains he was part of a unit sent to Africa to intervene in a civil war in 1997 - however, due to bad intelligence, they were dropped in the wrong place, with the brutal conditions and guerrilla attacks whittling them down to just four members by the time they reached the designated site. Which, in yet another intelligence foul-up, wasn't a guerrilla camp at all, but an innocent village.
However, his commanding officer snapped and ordered Billy's unit to massacre the villagers. In flashback, Billy remembers trying to stop the madman, only to be knocked unconscious; the unit killed the villagers and then blamed Billy for it when they returned to America. For his own reasons, he doesn't tell this to Rebecca, dismissing the past as the past. He doesn't believe he has any chance of a fair hearing; as he tells Rebecca, his only choices are to turn himself in and be executed, or run as long as he can.
The discussion ended, the two resume exploring the sub-basement levels. Finding three stone plates adorned with Umbrella's watchwords - Obedience, Discipline, Unity - they ultimately make their way to the observatory. Here, a device reacts to having the three plates fitted into it by partially rotating the observatory tower, allowing them access to a previously cut-off chapel.
Although it is guarded by a giant bat, the two make short work of it, and find a hidden elevator that descends into a lab facility beneath the church. Separating temporarily to explore the different levels, they battle both regular and leech zombies before reuniting. In a study, they discover an ancient black and white photograph of the strange man they saw in the Arklay forest - but this photograph is apparently a graduation photo of the original James Marcus, and is dated back to 1939! Needless to say, they figure that the man they saw must be Marcus's grandson.
Continuing their exploration, they find a promise of hope; a deactivated cable car. Once they retrieve the input and output regulators from their hiding places in the lab, they ready themselves to escape - only to be attacked by more of the mansion's monsters. An Eliminator knocks Billy over the railing and causes him to fall into a river far below, whilst Rebecca is attacked by a leech zombie. By the time she has dispatched her attacker, there is no sign of Billy. Distraught, but unable to do anything else, Rebecca rides the cable car to a facility somewhere else in the wilderness. Here, she activates a freight turntable and rides it down into an underground lab complex.
At this location, she meets up with Captain Marini, who tells her that they are not far from an old mansion. However, Rebecca refuses to accompany him, explaining she has to find Billy. Unable to convince her, Enrico leaves her, promising to wait for her at the mansion.
Within the next 48 hours, he will be dead, assassinated by his own teammate in the tunnels under the Arklay lab.
Rebecca takes a key spotted nearby and goes to activate an elevator at the far end of the turntable, only to find herself attacked by a deformed humanoid creature, one hand twisted into gnarled claws, its spine exposed. Though she doesn't know it, this is a prototype version of the Tyrant B.O.W that her teammates Chris and Jill will battle soon. Through luck and heavy firepower, she manages to put the creature down.
Riding the elevator down, she finds herself on a narrow bridge leading to a nearby sewer treatment facility. Here, she sees Billy, barely conscious but still alive, clinging to a twisted chunk of concrete and rebar in the middle of the water. She calls to him, but something in the water strikes at him, dislodging him and sending him flowing into a deeper part of the facility. Emboldened, Rebecca gives chase. She is unaware that the strange young man has watched her approach, and deemed himself no longer amused by her and Billy's struggles.
After fighting her way through yet more monsters and restoring power, she finally finds Billy in a treatment pool. Together, they resume exploring the facility, looking for a way out; after defeating the Proto-Tyrant, which wasn't quite dead and had managed to make its own way to the treatment facility, they ultimately make their way to the plant's incinerator. Here, they encounter the biggest swarm of leeches yet, and finally come face to face with the strange young man.
He reveals himself as Dr. James Marcus; his fellow Umbrella executive, Spencer, had him assassinated a decade ago, but as he lay dying, his precious mutant leech invaded his body and fused with it. After years of mutation and integration, the revived Marcus seeks revenge on Umbrella, and the destruction of the world.
Then, he transforms into a monster, a larger and more grotesque version of the leech zombies that they had been battling to this point. After a fierce firefight, they seemingly dispatch him and, locating a cargo elevator, begin riding to the surface. As they ascend, an automated voice suddenly blares, declaring that the self-destruct sequence has been activated. Worse, the Marcus leech has regenerated and transformed into an even bigger, more powerful and inhuman form, which barrels up the shaft under them, smashing through the elevator and cornering them in the warehouse above.
Rebecca and Billy struggle to drive it back with what firepower they have remaining, only to realize that the creature is averse to sunlight. Billy covers Rebecca as she activates the dials to open the roof, ultimately bathing the Queen Leech in sunlight. As it flails, knocking them sprawling, Rebecca finds an Umbrella special model Magnum Revolver, which she throws to Billy. One well-aimed shot, and the Queen Leech breaks apart at last into chunks, falling back down the shaft as the timer detonates and flames roar up from the subterranean level beneath. As the warehouse begins to collapse around them, the fire-forged allies flee for the exit.
In a single mighty explosion, Marcus' training facility, the sewer treatment plant, and all the horrors within are obliterated. Rebecca and Billy watch the destruction from a nearby grassy hill, Billy finally managing to pop his last handcuff free and throw it away. Once they have caught their breath, Rebecca spots the mansion that Captain Marini told her about, and makes a decision. She takes Billy's dogtags and informs him that she will declare him officially dead. The two salute each other, and separate at last. Billy heads south, hoping to find a road and hitchhike away from this mess. Rebecca heads north, aiming to enter the mansion and meet up with her squad.
She has no idea what she is walking into...
