Lizzie Samuels is Ryan's daughter and Mika's sister. She was first seen with other children naming zombies, and later at storytime. During the outbreak her father is bitten, and before dying he asks Carol to look after his daughters. Lizzie expresses intentions to stab his corpse in the head to prevent renanimation but is emotionally unable to. Carol later tells her she is weak and needs to toughen up. Lizzie later gets the flu and is forced into quarantine. Carol is disturbed by Lizzie's apparently personal connection with walkers.

When some infected residents succumb to the virus and reanimate, Lizzie rescues Glenn from a walker by leading it away. After being treated with medicine, she plays with Glenn's blood. When The Governor attacks the prison, she convinces the other children to help in the battle. She and Mika rescue Tyreese from two of The Governor's soldiers, after which she escapes with the children and Tyreese. Lizzie, Mika, Tyreese, and Judith get separated from Molly and Luke.

Lizzie also is very sure Sasha is dead. She also shows a disliking towards Tyreese. After Lizzie kills Mika, Carol and Tyreese realize that she is too psychotic to be kept around and had to be executed in order for Judith to be safe, so Carol leads her out to the fields to look at the flowers, and as Lizzie tried to apologize for having threatened Carol and Tyreese, Carol executed her.