Seattle medical resident Olivia "Liv" Moore is turned into a zombie while attending a boat party. She abandons her career and breaks up with her fiancé, much to the disappointment and puzzlement of her family. She discovers that if she does not periodically satisfy her new appetite for brains, she will turn into a stereotypically primitive and homicidal zombie. Instead of feeding by killing innocent people, Liv decides to take a job at the King County morgue and eat the brains of the corpses she autopsies. Her secret is guessed by her boss, Dr. Ravi Chakrabarti. Ravi soon becomes Liv's friend and confidant, and as a scientist, he is intrigued by her condition.

Whenever Liv eats a dead person's brain, she temporarily absorbs some of their personality traits and skills, and she experiences flashbacks of that person's life. In the case of murder victims, the flashbacks offer clues about the killer. Liv uses this new ability to help Police Detective Clive Babineaux solve crimes. Though she initially passes herself off as a psychic, Clive eventually learns the truth about her and zombies. Meanwhile, Ravi works to develop a cure for Liv's affliction, in the hope that one day she will be able to return to her former life.

Over the course of the first few seasons, the number of zombies in Seattle gradually increases, while various factions try to cover up their existence, fight them, exploit them, or protect them. At the end of the third season, a zombie-run private military company infects thousands of people in Seattle with the zombie virus and imposes martial law on the city to create a safe haven for zombies. The final two seasons deal with the struggles and conflicts of living under these conditions; Liv becomes the leader of a human smuggling operation bringing people who want to become zombies into Seattle.