Wounded in the line of duty, small-town Georgia sheriff Rick Grimes wakes from a coma to find the world infested by zombie-like "walkers." Alone and disoriented, he sets off in search of his wife Lori and their son Carl.
Rick soon encounters two other survivors — Morgan and his son Duane. Morgan explains that the undead are driven to eat the living. "One thing I do know, don't you get bit," Morgan says. Bites kill, then you become one of them. Morgan has seen the transformation first-hand. His wife was bitten then turned into a walker. Now, she haunts him and his son by frequently returning to the house where she died.
Rick takes Morgan and Duane to the police station, where they stock up on guns and ammunition. Rick is headed to Atlanta where supposedly a refugee center has formed and the CDC is working on a cure. Along with a rifle, Rick gives Morgan a walkie-talkie with instructions to check in daily at dawn — that's how they'll meet up later.
En route to Atlanta, Rick runs out of gas near a farmhouse, where he finds a horse to ride the rest of the way.
Meanwhile, Lori and Carl are living outside Atlanta in a camp with Shane (Rick's best friend and partner), and other survivors. Believing her husband dead, Lori has begun a romantic relationship with Shane, who has become the group's de facto leader.
In a deserted Atlanta, Rick is overwhelmed by hordes of walkers who topple his horse and force him to retreat inside a tank. Guided by Glenn, an adventurous young man who instructs him via radio to make a run for it, Rick grabs a gun and a grenade and flees for his life. Glenn then leads Rick to a department store, where they meet up with other survivors: Andrea, Morales, Jacqui, T-Dog and Merle Dixon — a redneck ex-con.
Rick handcuffs the volatile Merle to the store rooftop after Merle attacks T-Dog. Rick then hatches an escape plan, which involves Rick and Glenn smearing themselves with walker guts as camouflage. Having navigated through the crowd of walkers, Rick drives off in a cube van to evacuate the survivors while Glenn lures the undead with the sound of a car alarm in a hotwired Dodge Challenger.
Back on the rooftop, T-Dog accidentally drops the handcuff key down a ventilation pipe, then chains the access door shut so that the stranded (and furious) Merle will be relatively safe from hungry walkers.
Driving back to camp, Morales warns Rick about Merle's brother Daryl, who will be irate about his brother's abandonment.
Glenn arrives at camp first. Shane and Dale (an older survivor who owns an RV) chastise Glenn about drawing walkers with the alarm. Jim, another survivor, disconnects the alarm just as the cube van approaches.
Andrea tearfully reunites with her younger sister, Amy, as does Morales with his family.
Rick emerges from the van and is shocked to discover Lori and Carl living at this camp. The family is tearfully reunited. Later, around a campfire, Lori tells Rick she was told he would be medevaced to Atlanta. But it never happened. "Mom said you died," Carl says. "She had every reason to believe that," Rick replies before thanking Shane for saving them.
That night, Rick and Lori have sex in their tent, vowing to each other that this is a new beginning in their marriage. The next morning, Rick and the others find a walker feasting on a freshly-hunted dear in the woods. Jim theorizes the walkers are running out of food in the city.
Daryl returns from an overnight hunt. After being informed of his brother's whereabouts, Daryl attacks Rick and Shane who quickly subdue him. Daryl vows to retrieve Merle. "I'm going back," Rick volunteers. Glenn and T-Dog also enlist.
"You're putting every single one of us at risk," Shane replies, arguing they need everybody to protect the camp. What they really need, Rick contends, are the guns that he dropped when the walkers attacked. Lori is against it, but Rick tells her he has to get the walkie-talkie back, otherwise Morgan and Duane will walk into the same trap he did.
After Rick departs, Lori tells Shane to keep away from her family. "You are the one that told me that he died," Lori seethes.
Nearby, an altercation breaks out between a hulking survivor, Ed, and his meek wife Carol. After Ed slaps Carol, Shane intervenes and beats Ed to a pulp.
In Atlanta, Rick and company find the rooftop deserted save for a severed hand lying beside a hacksaw. They follow Merle's trail of blood down to the streets, but decide to retrieve Rick's guns before continuing the search.
Glenn goes for the guns while the others stand guard. Their plan is derailed when Daryl is jumped by two men, who eventually take Glenn hostage at an inner city fortress that turns out to be a nursing home. Glenn is set free and Rick passes on some guns to the nursing home staff for protection.
Rick, Glenn, T-Dog and Daryl discover their vehicle is missing. "Merle," Rick says. "He's going to be taking some vengeance back to camp," Daryl predicts.
Back at camp, Andrea and Amy present fellow survivors with fish caught at a nearby lake. Dale interrupts the excitement to express concern over Jim, who's feverishly digging holes without explanation.
Shane subdues Jim, who can't remember exactly why he was digging: "I had a reason, don't remember," he says. "Something I dreamt last night."
Andrea, meanwhile, roots through Dale's RV looking for something to wrap up Amy's birthday present: A necklace stolen from the department store.
Later, the group jovially feasts on fish around the campfire. When Amy steps away to go to the bathroom, she's bitten in the arm by an unseen walker — one of many about to attack the camp.
Rick and his cohorts arrive to drive the zombies back, though he's too late to save Amy or Ed. Jim is also bitten in attack.
The survivors burn walkers' bodies, though Glenn insists they should bury their dead. Andrea cradles Amy nearby, unwilling to let anyone near the body. Dale commiserates, explaining that since his wife's death, "you girls were the first people that I cared anything for."
Andrea tells Dale she feels guilty for missing so many of Amy's birthdays. "I'm sorry for not ever being there," Andrea sobs, shooting the now-walker Amy in the head.
When Jim's injury is revealed, Rick suggests the group go to the CDC for help. Shane thinks the Army base in Fort Benning, 100 miles away, is safer.
While sweeping the forest for walkers, Shane tries to convince Rick to change his mind. "I've gotta do what's best for my family," Rick says. "If it was your family you'd feel differently." Enraged, Shane aims his gun at an unknowing Rick, but comes to his senses.
Later, Shane announces his support of Rick's plan. Morales says that his family will not be joining the group and they head off in a different direction.
En route to the CDC, the RV breaks down. Jim, in agony, asks Rick to leave him behind. "I want to be with my family," he says of his late wife and children. The group reluctantly leaves him beneath a tree.
In a CDC laboratory, disheveled scientist Dr. Jenner performs experiments on tissue sample TS-19. He accidentally spills corrosive fluid initiating a decontamination sequence that destroys the sample.
Meanwhile, Rick's caravan approaches the CDC. Jenner watches the group's approach via a security monitor. He agrees to allow them into the building, provided they submit to blood tests.
The group feasts on food and wine, then luxuriates in hot showers. Afterward, Andrea laments the fall of civilization as Dale attempts to comfort her.
Later, Shane drunkenly confronts Lori, professing his love and insisting he did not lie about Rick being dead. (Indeed, at the outset of the walker outbreak, Shane visited Rick in the hospital where amid sheer chaos he attempted to rescue Rick, but failed). Drunk and out of control, Shane tries to force himself on Lori, who scratches his face and neck to stop him. Horrified by his own behavior, he flees, leaving Lori shaken and afraid.
The next morning, Jenner shows the group brain scans of his genius wife who allowed her infection to be recorded. He admits he doesn't know what the disease is or how to treat it. Plus, he's lost contact with other facilities. Worse yet, the CDC's generators are running out of fuel. When they're empty, the building will self-destruct as per a decontamination protocol.
Though at first he tries to convince them to stay, Jenner agrees to let Rick and the others flee when the self-destruct is activated. Jacqui, terrified of ending up like Amy or Jim, opts to stay behind. After a fiery explosion, Rick and his fellow survivors caravan away from the smoldering rubble, destination unknown.