History teacher Lee Everett is arrested for allegedly killing a state senator sleeping with his wife. While leaving Atlanta with the police, the police cruiser he is in runs over a zombie - or walker, as they are referred to in the series - and crashes off the highway. After fighting off the police man (who turned into a walker after the crash), Lee meets Clementine, a young girl, as well as Shawn Greene. Shawn takes Lee and Clementine home to the farm of his father, Hershel Greene. Lee meets a family, consisting of husband-wife Kenny and Katjaa, and their son Duck. After failing to save Shawn from walkers, Lee, Clementine and Kenny's family are banished from the farm.
The group heads to Macon, Georgia where they meet a group of survivors, led by a woman named Lilly, who save them from a herd of walkers and are situated in a drugstore which Lee's parents own. The group goes into a scuffle with Lilly's father, Larry, who quickly encounters a heart attack afterwards, and requires medication from a nearby pharmacy. Another member of the group, Glenn, decides to salvage for supplies in a motel, however he is stranded in the motel, leading Lee and news reporter Carley to rescue Glenn.
Glenn decides to help a stranded survivor named Irene, however Irene is revealed to be bitten and commits suicide upon taking Carley's gun. Upon returning to the drugstore, Lee comes to the conclusion that his parents were killed by walkers. Carley tells Lee that she knows Lee's past, but keeps his secret. Lee and IT technician Doug head out to find the keys of the pharmacy. Lee is forced to kill his reanimated brother in order to retrieve the keys. Upon entering, the alarm sounds, forcing the group to leave the drugstore after giving Larry medicine. Upon leaving, Lee saves either Carley or Doug from walkers, and he is knocked out by a vengeful Larry. Lee is rescued by Kenny, and the group heads to the motel for shelter.
Upon hearing Atlanta is overrun by walkers, Glenn leaves the group and heads for the city in order to rescue his friends left behind. Despite finding comfortable shelter and water, the group's glimpse of hope is short-lived when electricity is suddenly shut off, and a sneak peek of Episode 2 "Starved For Help." shows and then the ending credits roll after that and Episode 1 "A New Day" finishes.