History teacher Lee Everett is on his way to prison, having been convicted for killing a state senator who had slept with Lee's wife. While leaving Atlanta for prison, being driven by a police officer, the police cruiser he is in runs over a 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 who was hiding out in her tree-house, as well as Shawn Greene. Shawn takes Lee and Clementine home to Shawn's family farm, owned by his father, Hershel Greene. Lee meets a family, consisting of husband and wife, Kenny and Katjaa, and their young 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 saves them from a herd of walkers. Lilly's group is situated in a drugstore which Lee's parents owned. The group goes into a scuffle with Lilly's father, who quickly encounters a heart attack afterwards and requires medication from a nearby pharmacy. Another member of the group, Glenn Rhee, decides to salvage for supplies in a motel; however he is stranded in the motel, leading Lee and a 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 an 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 pharmacy, the alarm sounds, forcing the group to leave the drugstore after giving Larry his medicine. Upon leaving, Lee saves either Carley or Doug from walkers, and he is knocked down by 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.

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