This volume picks up after the events of Volume 1: Days Gone Bye. After the death of Shane, Rick Grimes and the rest of the survivors leave Atlanta and travel across many miles of hostile territory seeking a safer home. The group picks up new members and loses old ones as they attempt to survive the brutal winter. The group eventually finds shelter at a small farm, though it is discovered that Hershel Greene, the owner of the farm, and his family are keeping a dark secret.
Lori Grimes is having a flashback to the beginning of the outbreak, where she's waiting outside of Atlanta in a jammed line of cars, where she is confronted by Shane. Lori expresses her regret about leaving Rick behind at the hospital, but, expresses comfort about how Shane accompanied them. The two of them end up having passionate intercourse on the grass not far away from their car.
Back to the present, the survivors are burying Shane. Rick is still in shock over Shane's attempt to murder him and expresses worry about the mental stability of the rest of the group. Lori spits on Shane's grave. Dale then tells Rick that the group want Rick to be their new leader. Dale talks with Rick about Shane and tells him that Andrea thinks Christmas is coming up. Rick immediately tells Dale that he wants to skip Christmas this year so none of the kids get upset. Rick asks Carl if he wants to talk about what happened with Shane, but, Carl doesn't say anything. The group then departs from their camp using the RV. They continue on their journey until they need to clear some cars that are blocking the road. While clearing the cars, the group are surprised by the sudden arrival of Tyreese, his daughter, Julie, and her boyfriend, Chris. Rick nearly kills Tyreese after mistaking him for a roamer, but, the group quickly allow the new arrivals to join them. Lori is not happy about this and tells Rick not to be so trusting of other people, even if they have kids with them. The next morning, Tyreese and Rick are discussing how the apocalypse has drastically changed them and the people they know. Tyreese explains to Rick that a few weeks ago, while scavenging a nearby country store for supplies, an old man who was supposedly the nicest old man anyone could ever meet had been living in the store and attempted to rape Julie. However, he was able to kill the man before he could rape her. This reveals that, similar to Rick, Tyreese is willing to do what is necessary in order to survive, regardless of how gruesome it may be. Tyreese feels that the apocalypse has changed him even more than it had changed the old man as he feels no remorse for killing him. Rick later explains to Tyreese the names they gave zombies which were roamers (who are always on the move) and lurkers (who are content with sitting around all day until they smell or see food nearby) because not far ahead they see two roamers heading toward the group, Rick and Tyreese quickly and quietly kill the zombies, Rick uses his axe and Tyreese uses his hammer. The following night, the other group members are quickly warming to Tyreese especially Carol who starts to flirts with Tyreese, he evidently returns the feelings. Lori reveals to Rick that she believes she is pregnant and then she tells the group that she is pregnant. Everyone is happy for the Grimes family, but, they are all worried because of the lack of doctors and medical care. Dale quickly confronts Rick about the fact that the baby might be Shane's based on the timing, but, Rick cuts him off saying that he is aware of it, but, he can't bear the thought or he will lose his mind.
The group continues on their journey until they come across a group of houses enclosed by a fence, titled "Wiltshire Estates". The group decide to stay there since they think they will be able to start a new life there. Tyreese and Rick proceed to clear a house, but, Rick is attacked by two zombies. Tyreese hears Rick shouting for some assistance and Tyreese football tackles one of the zombies that was about to kill Rick. After they kill both zombies Tyreese reveals details about his past as an NFL player. This house that Tyreese and Rick cleaned out is loaded with canned goods and there are enough rooms for everyone to bunk with their families which leads them to think that they may have found a permanent sanctuary. They end up spending the night inside the cleared house. What they don’t notice is a snow covered sign at the entrance to the enclosure that reads "ALL DEAD DO NOT ENTER".
In the morning, Rick and Lori are discussing how Carl is handling their situation and also about how they are going to give the baby a happy life. Donna talks with Allen about how happy she has been lately, having taken hope from seeing Dale and Andrea overcome their losses, their new sanctuary and that they couldn't have found nicer neighbors. The group plans to split and clear each of the houses. Rick notices the sign while fetching a gun for Tyreese and, shortly after, the group is attacked by a big group of lurkers which had been hiding in the houses. Donna is killed in the attack, leaving Allen devastated. He wants the group to leave him behind, but, is convinced otherwise by Rick who tells him to think of his children, Billy and Ben. Tyreese and Rick return to the house for Chris and Julie (finding them on the verge of having sex) and they all manage to escape the massive horde by jumping on the roof of the RV. The group then narrowly escapes from Wiltshire Estates in the RV. The survivors continue on. Rick and the others show concern for Allen's deteriorating emotional state. As the group's food supply begins to diminish, Rick, his son Carl, and Tyreese go hunting for some food. During the hunt, Carl is accidentally shot by a farmhand called Otis who mistakes them for zombies. Rick nearly kills Otis in a fit of rage before realizing that Carl is still alive. Otis informs them that one of the people at the farm where he has been staying has medical experience. Otis leads Rick to the farm with Carl as Tyreese informs the group of Carl's accident.
At the farm, Hershel Greene manages to extract the bullet from Carl and save his life. Hershel invites the group to stay while Carl recuperates and introduces the group to his children: his oldest daughter Lacey Greene, his son Arnold Greene, his daughter Maggie Greene, and his youngest son Billy Greene. Hershel also introduces his twins Rachel Greene and Susie Greene, Otis, and Otis’ girlfriend, Patricia, who live up the road, but, are staying with Hershel and his family since Hershel's home is more safer for them.
As the group settle in, Andrea tries to talk with Allen about getting over Donna and not shutting down for the sake of his sons, but, this just makes Allen extremely angry. Sophia is relieved that Carl is fine and pecks him on the cheek. Dale talks with Lori about the fact that her baby might be Shane's, but, does not want her to tell Rick as Rick is the one stable person in the group and is needed to be their leader. After dinner, Glenn talks with Maggie about how he feels sorry that he didn't try to talk to Carol sooner and maybe start a relationship with her as he doesn't want to be alone forever. Maggie agrees to sleep with him as she doesn't want to regret anything either. Hershel converses with Rick about a permanent place for the group to sleep, but, tells Rick that he doesn't want to sleep in the barn as that's where he's keeps all his dead ones. Hershel explains to an angry Rick about his views of the zombies as still being living people and not wanting to kill them in case they suddenly turn back to normal, and he explains that his eldest son, Shawn Greene, is in that barn with also many neighbors and random zombies that wandered onto Hershel's Farm.
The following day, the group is practicing how to shoot firearms when Hershel stops them because the Thompson house is getting riddled with bullets across the way. A zombie then appears and Hershel attempts to get the zombie inside the barn. As Hershel opens the barn, a zombie suddenly falls through and opens the barn doors all the way, allowing all the trapped zombies to break out. Arnold saves his dad from being attacked, but, is bitten by his zombified brother. The group begins to kill the zombies as Lacey is torn apart by a few of them. Finally seeing that his son will never be normal again, Hershel takes Maggie's gun and shoots his three children to prevent reanimation. He briefly puts the gun to his own temple, but, is stopped by Rick.
The next day, Hershel discovers Glenn sleeping with Maggie and gets into an angry argument with her, but, he leaves them be for the time being. Rick and Allen talk about Donna while cleaning up the barn to sleep in. Rick asks Hershel if they can sleep in the house, but, Hershel angrily tells Rick that he expects the group to leave the farm soon. Lori angrily confronts Hershel, saying that Hershel is sentencing them to death by forcing them out. Hershel maintains that he has to look out for his own family. Lori says that if they weren't there with their guns they would all be dead and blames Hershel's stupidity on his children's deaths causing him to slap her. Rick and Hershel argue and eventually Hershel puts a gun to Rick's head to force them to leave. The group finally decides to leave Hershel's farm. Otis tries to talk with Hershel who is now convinced that he has lost his mind after nearly killing Rick. Glenn stays behind to pursue his relationship with Maggie. After some unsuccessful raids and hunting parties, and the group becoming increasingly starved, Dale and Andrea stumble upon an abandoned prison. Rick tells the group that they can clean it up and make a life here, and pronounces it home.