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History teacher Lee Everett has been arrested for allegedly killing a state senator who was sleeping with his wife. While leaving Atlanta with the police, the police cruiser he is in hits a zombie - or "Walker" as they are referred to in the series - and crashes off the highway. Lee regains consciousness sometime later, and after fighting off the reanimated police officer, he meets Clementine. Clementine's parents were in Savannah before the outbreak, and after hearing a tearful farewell from Clementine's mother on an answering machine, Lee determines that her parents are dead and decides to care her. Lee also meets Shawn Greene, who with a friend, takes Lee and Clementine home to his family farm, run by his father, Hershel Greene. There Lee meets another family, consisting of husband-wife Kenny and Katjaa, and their young son Duck. After failing to save Shawn from a walker attack, Lee, Clementine and Kenny's family are banished from the farm by Hershel.

The group heads to Macon, Georgia, where they are rescued by another group of survivors led by a woman named Lilly, who are taking refuge in a drug store owned by Lee's parents. There is a brief argument with Lilly's father, Larry, as he believes Duck has been bitten and will soon turn into a walker, after which Larry succumbs to a heart attack that requires medication; items that are locked away in a secure storage room. With some investigation, Lee will learn that his parents had been killed by walkers. Another member of the group, Glenn, decides to head for a nearby motel to siphon some gasoline but becomes stranded, forcing Lee and news reporter Carley to rescue him. Glenn makes them stay and help another trapped survivor named Irene, but she is revealed to be bitten and - regardless of Lee's actions - ends up killing herself with Carley's gun. After returning, Lee and IT technician Doug head out to find the keys for the pharmacy, and Lee is forced to kill his reanimated brother in order to retrieve them. Entering the storage room sounds the burglar alarm, attracting many walkers and forcing the group to abandon the store. Lee then saves either Carley or Doug from the walkers before departing. Larry, having received his medication, punches Lee in the face in an effort to prevent him from escaping, but Kenny rescues him.

The survivors gather at the motel. Upon hearing over the radio that Atlanta is overrun, Glenn announces he will be returning there to see if he can help his friends and family. Clementine tearfully tells Lee that the walkie talkie she would use to contact her parents was broken during the escape from the pharmacy. Larry informs Lee that he is aware of Lee's conviction as a murderer, and promises to tell the whole group if anything happens to Lilly or Clementine. The episode ends with the group hopeful about their new refuge until the electricity suddenly shuts off.