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The story begins when Deputy Sheriff Rick Grimes and his partner, Shane, are in a shoot-out with an escaped prisoner on a highway. Rick is shot in the shoulder during the incident and falls into a coma. A month later, Rick wakes up in a hospital, but finds it abandoned. After dressing himself, he explores the hospital, finding a corpse which falls backward into the opening elevator, as well as a cafeteria door blocked by a piece of wood. Rick removes the wood and opens the door only to find multiple zombies inside the room. One of the zombies lunges at Rick, which causes both of them to fall down a set of stairs where the zombie's head falls off.
Rick locks the door behind him to hold back the other zombies. Severely confused, Rick leaves the hospital and finds a bicycle. As Rick walks toward the bike he sees a zombie that has deteriorated to nothing more than bones. At this sight, Rick temporarily breaks down. Shortly after, Rick uses the bike to return to his home and finds that his house has been looted and that his family, Lori and Carl, is gone. Upon exiting his home, Rick is knocked unconscious by a boy (Duane Jones) with a shovel. The boy's father (Morgan Jones) quickly tells him that Rick is not a zombie, and they bring him inside. Rick wakes up and has dinner Morgan and Duane. Morgan explains to Rick the nature of the outbreak, explaining it had started just over a month ago. Rick finds out that, before the media shut down, the government told everyone to relocate to major cities in an effort to protect them. Rick decides that Lori would have taken Carl to Atlanta where her parents live. Rick, Morgan, and Duane go to the Cynthiana Police Department in order to get supplies. Rick gives Morgan and Duane some guns and a police car while changing into a police uniform, while filling a bag with guns to take with him. Morgan and Duane decide to stay behind while Rick plans to go search for his family in Atlanta. Morgan thanks Rick for his generosity, while Rick advises Morgan to make sure he uses his police equipment sparingly in order to return it in good condition when the outbreak is dealt with. However, their goodbye is interrupted when a zombie reaches for them from behind the parking lot fence. Rick nearly shoots it, but is stopped by Morgan, who advices him not to waste the bullet. Rick and the Jones' part ways. On his way out of Cynthiana, Rick returns to find the severely decomposed bike zombie and puts it out of its misery before. Shedding a tear, Rick continues to Atlanta.
On his way to Atlanta, Rick's car runs out of gas forcing him to scavenge for gasoline at a nearby ranch. Inside the home, Rick finds the remains of a family that committed a religiously motivated group suicide. After throwing up from their smell, Rick continues to explore the property when he finds a horse and hatchet inside the family's barn. Rick takes the hatchet and horse out of the barn, planning to use the hatchet as a weapon and the horse to get to Atlanta in place of his incapacitated vehicle. Rick talks to the horse, reminiscing about how things were before the outbreak. He recounts to the horse the events of the day his son, Carl, was born, stating it was the happiest day of his life. As he continues into the emotional climax of laying eyes on his son for the first time, Rick realizes that thinking about the good old times makes the outbreak seem much worse, opting for silence for the remainder of his trip.
Rick arrives in Atlanta and enters the city, only to find it in ruins. As he progresses into the city, zombies begin to congregate and swarm him, knocking him off of his horse. As he sees his horse being eaten by zombies, he begins shooting and bashing oncoming zombies, shouting out "What's the matter with you!?" He runs into an alley where he meets a supply runner named Glenn. Glenn tells Rick to stop using his gun, as it will attract the entirety of the city's zombie population. Glenn advices Rick to follow him onto a building using its fire escape, then hop over an alleyway to another building from which they descend. Rick and Glenn exit the city safely as Glenn explains to Rick that the government's plan to herd everyone into the cities only "put the meat in one place," resulting in everyone in the city dying in under a week. Rick momentarily breaks down, deducing that his family must have been killed. Glenn then explains to Rick that there is a camp outside of the city where a group of survivors live, explaining there is a chance his family might be there.
When Rick and Glenn get to the camp, Rick is reunited with his wife, Lori, and his son, Carl. He is also reunited with his partner and best friend, Shane, who has been protecting Rick's family since the outbreak. Shane introduces Rick to the other survivors at the camp; Allen, Dale, Jim, Carol, Sophia, Amy, Andrea, Donna, Billy, and Ben. Allen and Donna are husband and wife and Ben and Billy are their twin boys. Carol is the mother of Sophia. Amy and Andrea are sisters. Lori explains to Rick that Shane guided Lori and Carl to Atlanta to stay with her parents, believing it to be the safest place for Carl, also believing Rick to be safe at the then-operational hospital. She continues to explain how the group set up the camp, stating that most of the people at the camp were late-comers to Atlanta that found the city impossible to enter. That night, Rick and Lori mull over everything that has happened, and Rick admits to how scared he has become now that he has reached his objective.
The next day, Dale warns Rick to be careful around Shane, believing Shane is in love with Lori and disappointed she has been reunited with her husband.Rick brushes it off, muttering to himself about Dale being just a "crazy old man." Rick and Shane go hunting while Lori, Donna, and Carol wash the laundry. The women discuss how Lori first met Rick and have a brief argument about their gender roles. Rick and Shane stumble across a zombie eating a deer, getting up close without the zombie noticing while making observations about its habits. Meanwhile, as the women go back towards the camp after finishing their laundry, they are attacked by a zombie. Dale decapitates the zombie before it bites Donna, but they find that the head is still alive. The zombie that Rick and Shane were studying suddenly attacks them. Rick hits the zombie in the head with his ax. The two men hear a gunshot and race back to camp. Lori cries to Rick and relays the story concerning the zombie attack and how they had to shoot it to kill its head. As Rick and Lori embrace, Shane looks on with a jealous expression on his face. Later that night Rick and Shane talk about moving the camp to a safer area. Shane argues that they shouldn't move the camp because if the government starts cleaning up the outbreak, they would start with a major city, resulting in them being rescued sooner. Rick believes that the risk is not worth the reward, as they are very close to a huge zombie population and the weather is becoming colder. Rick finally agrees not to move the camp, but insists they need to find more guns to protect themselves.
The following day, Rick asks Glenn if he could come with him to get supplies in Atlanta to obtain firearms for the group. Jim, who happens to be the sole survivor from Atlanta, tells them the location of a gun store five blocks from where Rick and Glenn first met. Glenn disapproves of the idea, stating that the density of zombies that far into the city is too high for anyone to feasibly walk through. Rick comes up with a solution, taking Glenn to the zombie that he and Shane had killed the day before. Rick explains his theory that zombies don't attack each other because of the stink of their decaying corpses. His plan is to rub the zombie's body parts on their clothes so that they will smell like the zombies, making it appear that they are also undead to the zombie population. The plan works, and they are able to go deeper into the city to obtain the firearms. Unfortunately, while exiting the city, it begins to rain, washing the zombie stench off. This causes an attack by the zombies, forcing Rick and Glenn to sprint through the hordes surrounding them while killing any zombies that get in their way. While Rick fends off the zombies in the city, one of them bites Rick in the shoulder. Safely outside of Atlanta, Rick checks his shoulder only to realize that the zombie hadn't bitten through his jacket. As they head back to camp with the guns, Rick tells Glenn not to tell Lori about the zombie attack. Meanwhile, Shane and Lori discuss Rick's trip into the city. Lori is concerned about Rick's well being, while Shane wants Lori to come inside out of the rain, offering to "keep her company". Lori rebukes him, saying he needs to stop their affair now that Rick is back. Shane asks Lori about the night they spent together on their way to Atlanta, implying they had sex. Lori tells Shane that night was a mistake.
Over the course of the next couple of weeks, the group has target practice supervised by Rick and Shane with the guns that Rick and Glenn brought back from the Atlanta gun store. Andrea quickly proves that she is the best shot in the group. Rick allows Carl to practice with guns, causing Lori to become agitated. Later, Rick, Shane, and Dale go to the woods to collect firewood discussing Donna, who has been complaining about how sinful it is for Andrea and Amy staying in Dale's camper. Rick mentions that the weather is becoming colder, causing Shane to yell at Rick to shut up about the worsening winter conditions, leaving Rick speechless. While eating dinner that night Rick asks the others what their lives were like before the outbreak. Dale says that he was a retired salesman who was traveling with his wife in their RV when the outbreak came. Dale's wife died in the initial outbreak while they were at a campsite leaving Florida. After burying her, Dale came to Atlanta to find his cousins. He met Amy and Andrea stranded after their car had run out of gas. Andrea was driving Amy back to college so that they could have some bonding time. Andrea had a job as a clerk at a law firm, and Amy was going for her Physical Education major at college. Glenn was a pizza delivery boy who was swimming in debt and nearly forced to ask his estranged parents for money when the dead started rising. Knowing now he couldn't talk to them if he wanted to, he feels deep remorse. Allen ran a shoe store in a mall and was also struggling to make ends meet. Jim simply says that he was a mechanic. Finally, Carol talks about how her husband, a successful car salesman, committed suicide when he saw his parents being eaten by zombies. She also implies that he was abusive and simply convinced her to stay with him long enough to care for Sophia. Amy goes to the RV to use the bathroom when she sees a zombie, causing her to unknowingly back up into another zombie which bites her in the neck, killing her. The zombies are revealed to be just a couple of a larger herd laying siege to the camp, launching the survivors into a violent panic. Carol and Sophia are saved by Glenn as Andrea grieves over Amy's body, oblivious to everything. Lori is nearly killed by a zombie, but, is ironically saved by Carl, who shoots the zombie. Jim launches into a rage and attacks a zombie while repeatedly yelling that it killed his family. When all the zombies are dead Andrea shoots Amy in the head in order to prevent the reanimation. It is then revealed that Jim was bitten in the arm when he killed the zombie, though he says "it's nothing, it's just a scratch."
The next day a funeral is held for Amy. Shane, Donna, Dale, and Rick all take turns eulogizing her. Jim has perhaps the biggest speech, saying that nobody deserves this kind of death, especially a nice girl like Amy. Andrea is in a depression and Jim falls desperately ill. Meanwhile, Rick, Shane and Carl go hunting. Carl reminds Rick that they don't need as much food because Amy is dead and that Jim is too sick to eat, provoking Shane to yell at Rick, saying it wasn't his fault. When they return, Donna informs them of Jim's request to leave him outside of Atlanta. Jim hopes that once he turns, he can reunite with the zombified members of his family. The group bring him to the outside of Atlanta to say goodbye. The following day, Shane tells Rick to get ready to go hunting. Rick tells Carl to stay behind so that he and Shane can talk, prompting Shane to yet again start yelling at Rick about how it wasn't his fault Jim and Amy are dead, punching him. Lori then punches Shane, yelling "What's wrong with you!?", causing Shane to mentally snap and run off. Rick goes to follow Shane and Carl in turn follows his father. When Rick catches up to Shane, Shane starts yelling at Rick about how he just lost everyone's respect and how Lori would have changed in time and loved him if Rick hadn't returned. Shane then points his gun at a bewildered, defenseless Rick, yelling that he was never meant to come back. However, before he is able to shoot him, Carl shoots Shane in the neck, causing Shane to choke on his own blood until he dies. The book ends with Rick and Carl in an embrace, Carl saying "It's not the same as killing the dead ones, daddy," with Rick somberly replying, "It never should be, son, It never should be."