Robert Neville, a doctor, due to an experimental vaccine, is the only survivor of an apocalyptic war waged with biological weapons. The plague caused by the war has killed everyone else except for a few hundred deformed, nocturnal people calling themselves "The Family". The plague has caused them to become sensitive to light, as well as homicidally psychotic. They believe science and technology to be the cause of the war and their punishment, and Neville, as the last symbol of science, the old world, and a "user of the wheel", must die. Neville, using electricity, machinery, and science attempts to hold them at bay.

In Downey, the teenagers Chris, Scott and Tim are best friends and decide to drive to a bar downtown to a grungy band's gig. Chris' girlfriend Jackie, meanwhile, goes to a party with her preppy friends. While heading downtown, the trio of friends note that there are no cars on the roads despite the rush hour and then they find that the streets are empty. When they arrive in their destiny, they are chased by zombies and run to the bar. Chris decides to return to Downey while Jackie and her friends are attacked by a bunch of zombies.