After finishing a long shift as a nurse, Ana Clark returns to her suburban Milwaukeeneighborhood and her husband, Luis. Caught up in a scheduled date night, they miss an emergency news bulletin. The next morning, a neighborhood girl named Vivian enters their bedroom, looking mutilated. Luis approaches her to see what's wrong and she suddenly bites him on the neck. Ana locks Vivian out of the room and tries to tend to Luis who goes into shock, then dies. She attempts to call the hospital only to find that there is no connection; as she keeps ringing, Luis rises up, now infected with the same disease and immediately goes after Ana. She flees in her car and drives away, seeing chaos all around her neighborhood, but eventually crashes and passes out.
The intro scene rolls in, depicting riots and war in the major cities and the downfall of human civilization. Upon waking, Ana is confronted by Police Sergeant Kenneth Hall, electronics salesman Michael, petty criminal Andre and his pregnant wife, Luda and joins them, after they prove she is still alive. They break into a nearby mall and are attacked by a zombified security guard, who scratches Luda. Kenneth is also badly injured while wrestling with the zombie, which Ana subdues with his shotgun. They are then confronted by three living guards — C.J., Bart, and Terry — who make them surrender their weapons in exchange for refuge. They split into groups to secure the mall and then go to the roof where they see another survivor, Andy, who is stranded alone in his gun store across the zombie-infested parking lot.
The next day, a delivery truck carrying more survivors enters the lot, with zombies in close pursuit. C.J. and Bart wish to turn them away but are overruled and disarmed. The newcomers include Norma, Steve Marcus, Tucker, Monica, Glen, Frank and his daughter, Nicole. Another woman is too ill to walk; she is wheeled inside via wheelbarrow only to die. As Ana drapes her with a cloth, however, the woman reanimates and attacks her, getting stabbed with a poker. Ana theorizes with the group that the disease is passed by bites from the infected individuals, as she had already seen it happen with Luis. Andre leaves to see Luda, who has kept her scratch hidden from the group. They realize that Frank has been bitten and is a potential threat. After some debate, Frank elects to be isolated. When he dies and turns, Kenneth shoots him.
Over time, Kenneth and Andy start a friendship by way of messages written on a whiteboard; romance also buds between Ana and Michael (ultimately, consummating the relationship offscreen), and Nicole and Terry. One day, the power goes out. CJ, Bart, Michael and Kenneth go to the parking garage to activate the emergency generator and find a friendly dog inside. Zombies attack and kill Bart, forcing the others to douse the zombies in gas and set them ablaze. Meanwhile, Luda—tied up by Andre—gives birth and dies. She reanimates as Norma checks on the couple, killing the zombified Luda. Andre snaps; they exchange gunfire and both are killed. The others arrive to find a zombie baby, which they kill immediately.
The group decides to fight their way to the local marina, and travel on Steve's yacht to an island on Lake Michigan. They begin reinforcing two shuttle buses from the parking garage for their escape. However, they also need to pick up Andy, who is starving. They strap food and a walkie-talkie onto the dog, Chips, and lower him into the parking lot; the zombies have no interest in him. Chips gets into Andy's store safely but a zombie follows through the dog door, ultimately biting Andy. Nicole, fond of Chips, crashes the delivery truck into the gun store, where she is trapped by a zombified Andy. Kenneth, Michael, Tucker, Terry, and C.J. reach the gun store via the sewers and kill Andy, rescuing Nicole. They grab ammunition and go back to the mall. Along the way, Tucker breaks his legs and C.J. shoots him out of mercy. Once inside, they are unable to lock the door, forcing an evacuation.
Everyone boards the buses and navigate through the zombie infested city. Glen loses control of a chainsaw, accidentally killing himself and Monica; blood splatters on the windshield causing the bus to crash. C.J. exits the first van to look for survivors with Kenneth and Terry. They encounter the undead Steve but Ana kills him. She retrieves his boat keys and they take the remaining bus to the marina where C.J sacrifices himself so the rest of the group can escape. Michael reveals a bite wound and kills himself as Ana, Kenneth, Nicole, Terry, and Chips flee on the yacht.
Footage from a camcorder found on the boat begins with Steve's escapades before the outbreak and concludes with the group running out of supplies before finally arriving at an island, where they are attacked by another swarm of zombies. The camcorder drops, recording dozens of zombies chasing them.
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