This synopsis will spoil the events of all six films. You have been warned.
Dr. James Marcus, the original founder of the Umbrella Corporation, is searching for a way to cure his daughter Alicia's progeria. His efforts eventually bear fruit in the form of the Progenitor Cell. In Raccoon City, a boy whose disease was cured with medication derived from the Progenitor dies in a cable car ascending to the Arklay Mountain. His corpse soon reanimates and kills the other passengers. Umbrella covers up the incident, and Marcus's closest colleague—Dr. Alexander Isaacs—urges him to continue developing the Progenitor. When Marcus refuses, Albert Wesker kills him.
Marcus's death leaves Alicia with control over half of the Umbrella Corporation, though she is still a child, which means she cannot run the company. This leaves Isaacs in charge, and under his leadership, Umbrella becomes one of the most profitable corporations in the world. Isaacs develops an artificial intelligence program gifted with Alicia's image—The Red Queen—to help him run the company when it grows too large for even him to run. He also re-opens development of the Progenitor, which Umbrella eventually refines into the T-Virus.
Ten years later, the T-Virus is unleashed in The Hive, an underground research station that sits beneath the Midwestern town of Raccoon City. To keep the virus from escaping the facility, The Red Queen locks down and quarantines The Hive—then kills everyone inside. In the above-ground mansion that hides the entrance to The Hive, a young woman named Alice awakens in a shower after having been knocked out from the nerve gas released by The Red Queen. A few minutes later, a strike team bursts in and captures both Alice and Matt, a new Raccoon City PD recruit who had entered the mansion just before the strike team.
The entire group enters The Hive to find out what happened, and they encounter another survivor—Spence—on the way. The strike team then explains that everyone in the assembled group except Matt is an Umbrella employee, with Alice and Spence serving as security guards under the guise of a married couple living in the mansion. The commandos were sent by Umbrella to figure out why The Red Queen went homicidal. They have only a few hours to complete that task, too, because after the door to The Hive closes, it will stay closed.
Everything goes smoothly until the group reaches The Red Queen's chamber—where her defense systems kill four members of the strike team before being disabled. The remaining members of the group shut the AI down, which shuts down all power to The Hive, and its bioweapon containers, for a few moments. The group is soon attacked by reanimated corpses, with a couple of members dying and one of the commandos, Rain, getting bitten and infected with the T-Virus. The survivors decide to restart The Red Queen (albeit with a remote killswitch in her motherboard), and the AI leads them to a way out. The path leads them through danger and thins their ranks until they hit a dead end not far from the exit.
By this time, Alice and Spence have regained the memories lost as a side-effect of the nerve gas: Alice was helping Matt's sister obtain information on Umbrella so the siblings (both environmental activists) could take down Umbrella, while Spence had stolen samples of the T-Virus to sell on the black market and released the virus within The Hive to cover his escape. Spence gets away from the group and leaves them locked in a flooded room, but before he can escape for good, a Licker released by The Red Queen kills him. The AI also demands that Rain be killed exchange for opening the door. Alice refuses to kill Rain, and one of the last surviving commandos activates the killswitch, which unlocks the door by default.
The survivors board the train back to The Hive's entrance, but during the ride, they come under attack by the bioweapon from earlier. Matt suffers a massive wound in his shoulder from the creature while Alice tries to fight it off. She succeeds when Matt shoots a zombified Rain, who falls backward against a hatch release and drops the bioweapon onto the tracks below, where it dies. Alice and Matt leave The Hive, though Umbrella scientists capture the both of them inside the mansion. When Matt begins mutating, they decide to put him in "the Nemesis program".
The next morning, Umbrella agents decide to re-open The Hive and figure out what the hell went on down there. Once the doors open, a horde of bioweapons escape and attack the unprepared group. With the T-Virus now free to infect Raccoon City, Umbrella knows it has little time left before the whole city is overrun. Company agents work fast to evacuate top-priority employees—one of whom, Dr. Charles Ashford, helped create the T-Virus. His daughter Angela is on her way out of town when the van she is in gets into a wreck, leaving her stranded and alone.
As conditions deteriorate, the Raccoon City Police Department becomes overwhelmed, and suspended S.T.A.R.S. team member Jill Valentine recommends that everyone should get the hell out of the city before the city becomes Hell. Elsewhere, Alice awakens in a hospital and soon stumbles outside, where she notices the worsened conditions. By nightfall, Umbrella has sealed off all the major exits, and the city has indeed become Hell, with zombies quickly overrunning the populace. Deep inside the city, a group of Umbrella soldiers led by Carlos Oliviera fight alongside remaining S.T.A.R.S. members to keep the undead hordes at bay, but even their combined forces soon fail. A small group of survivors that includes Jill hides inside a church, where they are attacked by several Lickers; Alice bursts through a window on a motorcycle and kills the creatures. Around this time, Umbrella unleashes the "Nemesis", a massive bioweapon programmed to seek out and kill all remaining S.T.A.R.S. members—which it does, while leaving a survivor in civilian Lloyd Jefferson ("LJ").
Some time after losing members of the group (and having an encounter with the Nemesis), Alice and the rest of the survivors are contacted by Dr. Ashford, who offers them a deal: If they can find his daughter, he will give them transportation on a helicopter leaving Raccoon City. When the group realises that Umbrella's plans for the city are "nuke it and cover the situation up", they take the deal. Alice and her group meets up with the remaining Umbrella soldiers and LJ at Alicia's school; two members of the combined group die, but the survivors find Angela safe and sound. She reveals that she is infected with the T-Virus—her father helped craft the T-Virus as a way to cure a genetic disease inside of her—and that there is an anti-virus. Alice later reveals that she, too, is infected with the T-Virus.
Alice, Jill, Carlos, LJ, and Angela make their way to the helicopter, but are stopped just before takeoff by Umbrella goons. Major Cain, the head of Umbrella's containment operation, demands that Alice fight the Nemesis—which is actually Matt after having been mutated by the T-Virus and enhanced by Umbrella. When she refuses, he kills Dr. Ashford and threatens to kill the other survivors. Alice relents and fights the Nemesis in hand-to-hand combat; she eventually impales him on a metal pole, at which point she refuses to kill him. This awakens whatever is left of Matt, and the Nemesis turns on its masters by slaughtering numerous Umbrella soldiers and giving the survivors a chance to escape. Cain tries to escape with them, but Alice tosses him out and leaves him to the undead.
The helicopter lifts off shortly before Umbrella launches a nuclear missile toward the heart of Raccoon City, where it detonates and wipes out the entire city. Though they escape the blast, Alice and the survivors are forced into a crash landing, and Alice saves Angela from certain death by using her body to shield the young girl from a piece of debris. She is the only one found, and still barely alive, when Umbrella scours the wreckage. Over the next few weeks, the nuclear holocaust at Raccoon City becomes a top story—first because the actual cause of the blast is revealed, then because the (successful) cover-up on Umbrella's part paints those who broke the news as hoaxers.
When Alice eventually awakens in Umbrella's research facility in Detroit, Dr. Isaacs asks her if she remembers anything. She recovers her memories in short order—"I remember everything"—and escapes the facility, all while showing signs of supernatural abilities. Umbrella soldiers stop her after she exits the building, but Carlos and Jill, disguised as Umbrella operatives, take her away. Isaacs allows them to leave, then activates "Project Alice".
In the five years after the Raccoon City Incident, the T-Virus all but destroys the world. Both humans and animals become infected, and the virus's spread (as well as the side effects) turn once-lush natural environments into barren wastelands. Alice cuts herself off from most other survivors until she learns of a place called "Arcadia" that is said to be free of the T-Virus. She takes this information to a group of survivors that has old friends LJ and Carlos in addition to Claire Redfield.
(By the way, there is at least one good reason that Alice stayed away from other survivors: The novelization of Extinction reveals that Dr. Isaacs used Umbrella's cybernetic control over Alice to force her into bringing Angela to him. When he discovers that Angela's blood cannot help control the T-Virus ravaging the world because of differences in the strains, he orders Alice to kill Angela. A compliant Alice shoots the young girl in the head.)
The survivors travel to Las Vegas in an attempt to gather supplies, but they come under attack by a group of heavily-mutated zombies—the results of Dr. Isaacs trying to develop a cure for the T-Virus. Several survivors die in the battle against these new foes (including an infected-then-turned LJ), and Alice is stopped in her tracks by Isaacs and Umbrella's cybernetic controls. She eventually regains control of herself, slaughters the remaining zombies, and goes after Isaacs, who gets bitten by a zombie during his escape. Alice and the group follow Isaacs to another Umbrella facility, this one guarded by a large fence that keeps out a vast horde of the undead. An infected Carlos sacrifices himself to help the cause: He ramming a tanker truck through the undead horde and into the fence, then blows the whole thing up to clears a way for the survivors. Alice gets the rest of the group on the helicopter and urges them to find Arcadia, then enters Umbrella's underground facility for some payback.
When she arrives, she finds the place in ruins. Another holographic AI, The White Queen, explains that Isaacs had been doing research on a cure for the T-Virus, and Alice's blood was the key to developing one. The White Queen also reveals that Isaacs's T-Virus infection had grown too out of control; after he mutated, he destroyed everything in his path. Alice soon finds herself face-to-face with...herself—or specifically, a set of clones created by Umbrella in an attempt to re-create the original Alice and her specific blood strain. She faces off against Isaacs in a brief struggle and forces him into a deeper part of the facility.
Alice follows Isaacs, and she soon ends up in a replica of the mansion above The Hive (part of Isaacs's tests for the Alice clones). A heavily-mutated Isaacs attacks Alice with murderous intent, so she defends herself with her newfound telekinetic abilities. Isaacs overpowers her and sends her crashing into a recreation of the laser grid room from The Hive. He threatens to kill her, but Alice laughs after she realises where she is, saying that they will both die. The laser grid activates and slices Isaacs into tiny pieces; Alice escapes death when one of her clones shuts down the grid.
Four years later, Alice leads an army made up entirely of her clones into Umbrella's stronghold in Tokyo, Japan; acting Umbrella chairman Albert Wesker, prepared for this turn of events, escapes in a helicopter and leaves the clone army to die in a nuclear explosion. The real Alice, who had also prepared for this turn of events, tries to kill Wesker in the helicopter—but a better-prepared Wesker stabs her in the neck with a needle and injects her with an anti-virus, which turns her back into a normal person. The fight distracts Wesker long enough for the helicopter to crash into a nearby mountainside. Alice survives the wreck, though Wesker is nowhere to be found.
Six months after the wreck, Alice has finally made her way to Alaska, still searching for Arcadia and the other survivors. When she arrives at the supposed location of the safe haven, she finds wrecked planes and no survivors—save for Claire, who has come under the control of Umbrella. Alice destroys the mind-control device implanted on Claire's chest, which snaps her out of Umbrella's control but also leaves her an amnesiac. The pair fly down the West Coast to Los Angeles and find a group of survivors in need of help. Alice lands the plane on the roof of a large prison, where the new group of survivors wonder if Alice and Claire have been sent by Arcadia—which is not a fixed place, but a large ship which has now anchored off the California coast.
The prison survivors take Alice and Claire in, where they soon meet the prison's last remaining inmate: Claire's brother Chris. He claims he has been falsely imprisoned, and in exchange for his freedom, he will show them a way out of the prison. Several zombies bust into the prison through a hole in a shower room and kill one of the survivors, so the group frees Chris in exchange for his information. He reveals that the prison has a giant armored vehicle that can hold everyone, and it is sitting near the front gates. Chris and Alice swim through several flooded areas to reach the prison's armory, where they stock up on guns and ammo, while the other survivors reinforce the front gates from a massive bioweapon attack and find the armored vehicle—without its engine. One of the survivors, Bennett, shoots another survivor and goes back to the prison roof. He escapes using Alice's plane and heads for the Arcadia.
After regrouping, Alice and her allies decide to use the tunnel created by the zombies in the shower room to escape. Before Alice and Claire can make it out, an Axeman attacks them; working together, the two women dispatch the behemoth, then follow their friends into the tunnel. When they get out of the other side, only Chris is waiting for them; the other survivor, Luther, was dragged back into the tunnels. The Redfields and Alice make their way to the Arcadia, but when they board the ship, they find no crew despite the ship being otherwise functional. Before delving into the cargo holds, Claire gets her memories back—notably, the memory that Arcadia was a trap set by Umbrella to capture survivors for further T-Virus testing. The trio soon find themselves face-to-face with Bennett, who was working for Umbrella all along, and his boss...Wesker.
Wesker reveals that he needs "fresh DNA" to keep his mutations in check, and the Arcadia crew abandoned ship when he started eating test subjects. The Redfields try to take Wesker down, but he quickly subdues the both of them before turning his attention to Alice. She takes down Bennett with the help of a freed survivor, then blows a hole in Wesker's head with a shotgun. She then frees the Redfields, who empty their guns into Wesker for good measure. This still does not stop him, as he manages to regenerate, devour Bennett, and hijack one of the escape planes. But when Wesker tries to detonate the Arcadia's nuclear self-destruct explosive, he learns that Alice packed it onto his plane instead; he manages, but only barely, to escape the blast intact. Alice and the Redfields free all the other survivors aboard the Arcadia, though they soon come under attack by a horde of Umbrella soldiers led by a mind-controlled Jill Valentine.
The soldiers capture Alice and take her to an unknown facility, where she is interrogated by Jill for an unknown period of time. While resting from another round of audio-induced torture, the power in the facility goes out, giving Alice a chance to escape. She leaves her cell and runs down the hall, only to end up in Tokyo—or rather, as she later learns, an impressive recreation of the city's Shibuya Square. A small horde of zombies rush Alice, who defeats them in short order. She enters a control room for safety, but runs into Ada Wong, who has been sent to retrieve Alice on the orders of Albert Wesker.
According to Wesker, the Red Queen has control of Umbrella and wants to wipe out humanity, which means only Alice can help him stop it. Umbrella put Alice in an underwater facility beneath Russia—the same facility used to demonstrate the effects of the T-Virus for various countries, thus creating a global arms race for the virus. It now serves as Umbrella's last major stronghold, so to get Alice out, Wesker sent Ada in. Another strike team, which includes Leon Kennedy, Barry Burton, and Los Angeles survivor Luther, plans to rendezvous with the two women and help them escape. Before the team enters the facility, they set an explosive charge with a timer—an assurance that, regardless of whether the mission succeeds, the facility will be destroyed.
Ada and Alice go through a New York simulation (and defeat two Axemen along the way) before making their way into a simulation of a typical suburban neighborhood. Leon and his crew fight against a new form of zombie—the Las Plagas undead—as they look for a way out of a Moscow simulation. In an otherwise abandoned house, Alice finds Becky, a young deaf girl who survived a prior simulation where a clone of Alice was the child's mother. As Ada and Alice leave the house, a group of Umbrella operatives—led by clones of Rain, Carlos, and other members of the original Hive cleanup crew—stop them. The soldiers offer the trio a chance to surrender before opening fire. They lay waste to the house in a one-sided firefight; Alice and Becky escape, but Ada stays behind.
After encountering a friendlier clone of Rain (also from an earlier suburbia simulation), Alice rescues Leon and the remaining members of his team. The unified group heads toward the facility's exit, but are stopped from leaving by both the cloned soldiers (who have taken Ada prisoner) and a Licker (which kidnaps Becky and kills the "good" Rain). Barry sacrifices himself so the others can escape, and Alice manages to save Becky, though not without the girl learning about Umbrella's human cloning operation—and how her mother was, in fact, a clone.
Alice, Becky, Leon, and Luther all make it to the surface before the explosive goes off, which causes enough damage to flood (and thus destroy) the facility. But as they travel along the ice, their armored snowmobile is toppled by a surfacing submarine. Jill and the "bad" Rain, who are still holding Ada prisoner, emerge from the sub to fight Alice, Leon, and Luther. Rain infects herself with the Las Plagas parasite and fights the men while Alice goes one-on-one with Jill. Neither fight goes well for the good guys: Rain kills Luther with a punch strong enough to stop his heart, and Jill nearly kills Alice with enhanced abilities granted by Umbrella's mind-control device. Alice saves her own life by ripping the device off Jill, then saves Leon by shooting the ice beneath Rain and sending her into the water, where several zombies drag her down with them.
The survivors make their way to Washington D.C.; after entering the White House, Alice meets with Wesker, who injects her with the T-Virus again. He says that needs the "enhanced" Alice back if humanity is to have any hope left. He takes the survivors to the roof of the building, where a gigantic horde of bioweapons has surrounded them. "This is humanity's last stand", Wesker says.
That turns out to be a lie. Wesker had lured in everyone that could be considered a threat to Umbrella so he could wipe them out; only Alice seems to have survived whatever Wesker pulled off. (The novelization properly addresses Wesker's betrayal and the fates of the other survivors.) During her search for other survivors, Alice hides from the undead in an abandoned building, which is where The Red Queen contacts her. The AI reveals that Umbrella has created an airborne anti-virus that will kill the T-Virus and every organism infected with it. To retrieve it, Alice must make it to Raccoon City and re-infiltrate The Hive...and she must do so within forty-eight hours, as Umbrella plans to wipe out the remaining remnants of humanity around the world. Alice remains skeptical of the AI's claims until it offers her something else: a chance at revenge on Wesker and his superiors.
As Alice travels to Raccoon City, she is captured by Umbrella soldiers, who are working under the direct orders of Dr. Alexander Isaacs. He reveals that Alice had killed a clone—he is the one true Isaacs. He tries to kill Alice by pushing her out of a moving vehicle with a horde of undead behind it, but she eventually escapes and uses a stolen motorcycle to ride into Raccoon City. Alice later teams up with another group of survivors, this one led by Claire Redfield, and helps them fight the combined forces of an Umbrella convoy and a horde of undead. With no defenses left after the first attack and a second convoy/horde combination closing in, the group enters The Hive.
The Red Queen briefs the remaining survivors on the situation once they get inside: Isaacs and the other Umbrella executives planned the entire T-Virus outbreak to destroy humanity so they could rebuild the world in their own image. Although the AI was programmed to value human life—hence the original quarantine of The Hive a decade prior—it cannot hurt any Umbrella employee, hence the need for Alice. Before the group leaves to find the anti-virus, The Red Queen warns them that there is a traitor in their midst.
Wesker employs several traps within The Hive to split up and kill members of the group; Alice and Claire, as well as a survivor named Doc, all manage to survive despite Wesker's best efforts. As Alice and Doc travel to the lower levels of The Hive, they see the cryogenic chambers that are holding Umbrella's executives, who are waiting out the apocalypse. The pair rig up explosives that, once detonated, will destroy all the chambers and kill the executives. Once they reach the lowest level of The Hive, Alice and Doc hear a voice call out to them. It turns out to be Dr. Isaacs—the actual Isaacs, awakened from his cryogenic slumber so he can watch his victory first-hand.
Isaacs asks the pair to drop their weapons. Alice does, but Doc does not, revealing himself as the traitor. Wesker arrives with Claire as his hostage. Alice tries to figure out some way of killing Isaacs and retreiving the anti-virus, but he tells her not to bother because she would never be able to do it in time. Isaacs then reveals that Alice herself is a clone—of Alicia Marcus, whose body has aged rapidly, leaving her an old woman. He has been waiting for Alicia to die so he can run Umbrella himself, but so long as she lives, she retains control over half the company. Alicia uses her stake in the company for something good: She fires Wesker, which allows The Red Queen to close a giant door on his legs and keep him pinned down. Isaacs escapes, but before going after him, Alice gives Wesker the detonator to the bombs—a dead man's switch—and Claire kills Doc for his betrayal.
The duo corner Isaacs in an elevator, though when they try to fight him, he outfights them thanks to cybernetic implants that have enhanced his abilities. He incapacitates Claire during the fight, so when the elevator stops and he runs for his life, Alice goes after him alone. Isaacs traps Alice in another laser grid corridor, then activates the grid in an attempt to kill her. She dodges all the lasers, which forces Isaacs into hand-to-hand combat with her. A few strong blows later, he manages to cut off some of Alice's fingers with one of the laser grids. On the edge of defeat, Alice laughs...and holds up the pin to a grenade hidden in Isaacs's pocket. The grenade explodes and sends Isaacs reeling to the ground. Alice grabs the anti-virus from his pocket and heads for the exit. Just as she reaches it, Wesker drops the detonator; the explosives destroy the facility and kill all of the Umbrella executives.
Alice tries to release the anti-virus, but a still-living Isaacs catches the vial before it hits the ground. As he holds Alice at gunpoint, he is approached by his own clone—the Isaacs that led the earlier convoy—who wonders how the hell this could be happening. The real Isaacs tells the clone that he is a clone; the distraught clone attacks and kills the real deal, then dies at the hands of the undead. Alice shatters the vial of anti-virus and releases it into the air; every infected being in the nearby vincinity dies, including Alice.
...or not, as she is awakened some time later by Claire, who escaped the facility as well. She gives Alice a small device that lets her talk to The Red Queen, which tells her that the anti-virus destroyed only the T-Virus cells within Alice. The AI also reveals that before her death, Alicia Marcus made a copy of all her memories for Alice—a chance for Alice to experience a childhood she never had while being the woman Alicia could never become.
The anti-virus is an airborne agent, so it will require years to fully spread across the world and eliminate the T-Virus. (The T-Virus spread as quickly as it did because of typical human travel patterns.) Until such time as the virus is destroyed for good, Alice roams the land to search for survivors and wipe out anything still infected. Her first stop: New York City.
