After finishing a long shift as a nurse at the Milwaukee County Hospital, Ana returns to her suburban neighborhood and her husband Louis. Caught up in a date night, they miss an emergency news bulletin. The next morning, a girl from the neighborhood enters and kills Louis, who immediately reanimates as a zombie and attacks Ana. She flees in her car, crashes, and passes out. Upon waking, she joins police sergeant Kenneth Hall, electronics salesman Michael, petty criminal Andre and his pregnant wife, Luda. They break into a nearby mall and are attacked by a zombie security guard, who scratches Luda. Three guards — C.J., Bart, and Terry — make them surrender their weapons in exchange for refuge. They split into groups to secure the mall. On the roof, they see another survivor, Andy, who is stranded in his gun store across the zombie-infested parking lot.
The next day, a delivery truck carrying more survivors enters the lot, pursued by zombies. They include Norma, Steve, Tucker, Monica, Glen, Frank and his daughter, Nicole. Another woman is too ill to walk; she is wheeled inside, only to die and reanimate. After she is killed, the group determines the disease is passed by bites. Luda keeps her scratch a secret from the group, though Andre knows. Frank, who has been bitten, elects to be isolated. When he reanimates, Kenneth shoots him.
Kenneth and Andy start a friendship by way of messages written on a whiteboard; romance buds between Ana and Michael, and Nicole and Terry. When the power goes out, a few of the survivors go to the parking garage to activate the emergency generator and find a friendly dog who is adopted by Nicole and named Chips. Zombies 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 and Norma kills Luda. This makes Andre snap; he exchanges gunfire with Norma and the two kill each other. The others find a zombie baby, which they kill reluctantly. The group decides to fight their way to the marina and travel on Steve’s yacht to an island on Lake Michigan. They reinforce two shuttle buses from the garage for it; welding on a snowplow, attaching metal bars and chains as well as stocking chainsaws, propane tanks and road flares.
To rescue Andy, the group straps supplies onto the dog, Chips, and lower him into the parking lot; the zombies have no interest in him. Chips enters Andy’s store safely, but a zombie follows and bites Andy. Pursuing Chips, Nicole crashes the delivery truck into the gun store, where she is trapped by a zombified Andy. A group of them reach the gun store via the sewers, kill Andy, and rescue 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 because Steve temporarily abandoned his guard duty. Zombies storm the mall, forcing an evacuation via the buses.
While navigating the city, Glen loses control of a chainsaw, accidentally killing himself and Monica. In the chaos, their bus crashes. Steve tries to flee on his own but is ambushed by a zombie. Ana kills the zombified Steve and retrieves his boat keys. At the marina, C.J. sacrifices himself so the others can escape. Michael, after revealing a bite wound, kills himself as Ana, Kenneth, Nicole, Terry, and Chips flee on the yacht. Footage from a camcorder found on the boat shows the group runs out of supplies, arrives at an island and is attacked by a swarm of zombies. The camcorder drops leaving their fate unknown.