Alice (MILLA JOVOVICH) was the former head of security at The Hive, an underground and top secret research facility for experimental viral weaponry for the Umbrella Corporation. Unfortunately for her and everyone else working there, a virus got loose and infected most everyone, turning the dead into zombies hungry for the non-infected. Only Alice and another man managed to survive, but they were captured and experimented on by Umbrella Corporation scientists.
When Alice awakens, she finds the place deserted and Raccoon City infested with the undead. The government has cordoned off access to the city, carefully checking all who enter. This process is policed by the corporation's Special Tactics and Rescue Services team where the likes of Carlos Olivera (ODED FEHR), Jill Valentine (SIENNA GUILLORY) and Sgt. Peyton Wells (RAZ ADOTI) try to keep the peace.
After an infected person is found at the checkpoint, however, the city is sealed off, leaving them and TV reporter Terri Morales (SANDRINE HOLT) trapped among the many zombies. As Carlos and his team try to fight off the attackers, Jill, Peyton and Terri seek refuge in a church, but their sanctuary is short-lived. That's when Alice -- whose genetically altered body has left her with superhuman strength and related combat abilities -- rescues them. Yet, they must not only deal with the zombies, but also a seemingly indestructible genetic mutation -- named Nemesis -- that's being controlled by Maj. Cain (THOMAS KRETSCHMANN) who has an unusual interest in Alice.
While dealing with all of that, they get a chance to escape when wheelchair bound scientist Dr. Ashford (JARED HARRIS) offers to get them out in exchange for them finding and rescuing his middle school student daughter, Angie (SOPHIE VAVASSEUR), who's hiding somewhere in the city. They agree and, joined by civilian L.J. (MIKE EPPS), attempt to find the girl and get out before a planned nuclear attack kills them and everything else in the city.