Ana, portrayed by Sarah Polley](/actor/sarah-polley), is a dedicated nurse who, after working a tiring shift at her Milwaukee County hospital, returns to her tranquil suburban life with her husband Louis (Justin Louis). Their intimate evening takes a shocking turn as they miss early warnings from the media about a rapidly spreading, ominous contagion that transforms people into vicious, flesh-eating zombies.
The next morning, their lives are forever altered when Ana is roused by her zombified neighbor, Vivian, who attacks and fatally bites Louis. In a frantic attempt to save herself, Ana locks the door, but Louis succumbs to the infection and reawakens as a ravenous zombie, forcing Ana to escape through the window. Fleeing her chaotic neighborhood in a car, she crashes into a tree after an attempted hijacking, and we witness the catastrophic downfall of civilization through the opening credits.
Seeking safety, Ana encounters Kenneth, a hardened police sergeant played by Ving Rhames, who is trying to reach the nearby Fort Pastor army base. With their route blocked by zombies, they break into the Crossroads Shopping Mall along with three other survivors: the resourceful Michael (Jake Weber), the small-time crook Andre (Mekhi Phifer), and his pregnant wife Luda. Their initial encounter with a zombified mall security guard results in injuries; Luda receives a bite and Kenneth suffers a cut to his arm.
Inside the mall, they confront three living security guards—C.J. (Michael Kelly), Bart (Michael Barry), and Terry (Kevin Zegers)—and agree to submit their weapons in return for protection. As they secure the premises, they join forces with Andy, a survivor stranded in his gun store across the zombie-infested parking lot.
The next day, a delivery truck brings an array of new survivors, including the obnoxious businessman Steve (Ty Burrell) and the elderly Glen (R.D. Reid). They share dire news: Fort Pastor has been overrun and there’s no hope of rescue. After an encounter with a severely injured woman who soon reanimates, the group realizes that bites are the primary means for the undead to proliferate. Tensions rise when Ana and Michael clash over how to handle Frank, another victim of the contagion.
As life in the mall becomes increasingly complicated—relationships blossom, the undead circle in tighter—the darkness sets in. When the power goes out, a group ventures into the underground parking garage, where a friendly dog named Blue is found, but their relief is short-lived as Bart suffers a bite, and chaos ensues.
As Andre comes to terms with Luda's condition, he succumbs to despair, leading to devastating choices that result in their tragic end. Amidst a memorial where Kenneth states that "anything is better than sitting around waiting to die," they plot a daring escape across the water to an island. They rig up buses for protection and stock up on weapons, but the journey is fraught with peril and loss.
The situation escalates into pandemonium as they face overwhelming zombie hordes, leading to heartbreaking sacrifices, near escapes, and confronting personal demons. As they board the boat, Michael, having been bitten, makes his final choice leaving Ana and the remaining survivors to face an uncertain fate on the open water.
As the credits roll, we witness a grim epilogue: a recording from Terry's camera capturing the survivors’ desperate bid for survival as they reach an island, only to face yet another terrifying onslaught from a new wave of zombies, leaving the question of their survival hanging in the air.
