You play as Frank West, a freelance photo-journalist, and you're on a hunt for the scoop of a lifetime. Following a lead to the town of Willamette, he finds that the town has been practically taken over by zombies. Trying to get away, Frank makes his way to the Willamette shopping mall hoping he can find help there.

Gameplay takes place in a set seventy-two-hour period where one hour of real time equals twelve hours in game. Frank can freely move about the entire mall, though some areas are not accessible in the beginning. Most of it is infested with zombies, but he has a safe base in a security room. Players can follow the main plot, where they must be in the right place at the right time and successfully complete missions in order to advance, or do side missions, wander around killing zombies and dressing up in clothes from the mall stores, or just stay on the roof and wait for the helicopter to come back to pick him up. The helicopter comes at the end of the three days and the game is over regardless of whether Frank is on the roof to get rescued.

Frank gains experience by taking pictures, rescuing survivors and killing zombies. As he gains experience, he levels up, which gives him new moves, a larger inventory and more health.

Pictures are scored based on the number of survivors or zombies, their proximity to the camera and on emotional content, like horror, humor or sexiness.

Survivors are located throughout the mall and Frank must show up at the right time to rescue them. If you show up too early, they may not be at their location yet and if you show up too late, they will be dead. Frank can lead survivors back to the safety of the security room so they can be rescued. To do this, he can equip them with weapons and order them to follow him or wait at a specific location.

Rescuing survivors is complicated by the huge crowds of zombies roaming around the mall. There can be up to one thousand on screen at a time. Frank must avoid getting bitten and make sure the survivor continue to survive as he leads them. In addition to the zombies, Frank must face off against psychopaths, who are human who snapped when they saw the zombies and have become crazed killers.

Almost anything in the mall can be picked up and used. Food items restore health. Also everything else can be used as a weapon. Obvious, it's far more effective to kill zombies with a sub-machine gun or a chainsaw than by throwing CDs at them or hitting them with a mannequin, but you do have options and you may have to resort to killing zombies with a bowling ball or with you bare hands because all weapons have limited ammunition or durability and will eventually run out. You can pick up books from bookstores. These give you bonuses, like increased durability for a class of weapons, while in your inventory. There are also several vehicles you can use.

In keeping with the real-time theme, you are only allowed one save slot. Frank can save in bathrooms and in the security room, but this will overwrite and previous saves. If you make a mistake, you have to either restart the game, though you keep your current levels, or live with it and move on. This means your decisions do have consequences.

Once you complete the main plotline, you go into overtime mode, where Frank, rather than getting on the helicopter, gets another twenty-four hours to resolve the plot. If you beat overtime mode, you get infinite mode, where the helicopter isn't coming back, Frank loses health over time and all the survivors are trying to kill him. The object here is to stay alive as long as possible.