Clayton Riddell, a struggling artist from Maine who is estranged from his wife, Sharon, and his young son, Johnny, has landed a graphic novel deal in Boston. As he prepares to celebrate, somebody, somewhere, triggers "The Pulse," a signal sent out over the global cell phone network that instantly turns all cell phone users into bloodthirsty, homicidal creatures. Civilization crumbles as the Pulse's victims—dubbed "phone crazies" or simply "phoners"—attack each other or any unaltered people in view.
Amidst the chaos, Clay is thrown together with Tom McCourt, a good-natured man about Clay's age. The two decide to find shelter at the hotel that Clay was formerly staying at, where they meet an employee (referred to as Mr. Ricardi) who lets them inside after some minor arguments. Before they enter, Clay notices a girl standing across the street, but who at the sight of him runs away. Mr. Ricardi reveals that he had already shut off the elavator systems and blocked off the staircase with luggage in order to block off the guests that were turned into phone crazies.
Suddenly, the girl that Clay had noticed begins to pound against the hotel doors, pleading to be let in. She is being chased by a phone crazy, whom Clay kills after letting the girl inside. The girl, Alice Maxwell, explains that her mother owned a cell phone and was turned into a phone crazy while the two were riding in a taxi cab. Alice managed to escape before her own mother could kill her, and since then had been in a sort of catatonic state. Explosions echoeing outside, Clay advises that the four leave Boston, for fear that in time it will burn to the ground. Alice and Tom agree, but Mr. Ricardi is hesitant and decides to stay.
The three head towards a deli across the street to find food for the upcoming trip. Before leaving, Clay remembers that he left his portfolio of drawings in the hotel and upon returning to retrieve it, discovers that Mr. Ricardi had commited suicide, much to Clay's disdain. Clay informs Alice and Tom of Mr. Ricardis fate before the three make plans to travel to Tom's house in Malden to take shelter. As they leave Boston, they discover that the city had in fact, burned to the ground.
Upon arriving at Tom's house, the three take shelter and prepare for sleep, with Clay taking watch. However, Clay is woken by Tom to reveal that three phoners have broken into Tom's garden and are eating his vegetables. After a while, a phoner kills an elderly phoner before the two remaining phone crazies flee to the front yard, where Clay, Tom and Alice discover a large number of migrating phone crazies, only to disappear once again at dusk. They also begin to regain a semblance of intelligence, and forage not only for food, but also radios and CD players. Despite these developments, Clay is determined to return to Maine to rescue Johnny. Having no better alternatives, Tom and Alice come with him. They trek north by night across a devastated New England, having fleeting encounters with other survivors and catching disturbing hints about the activities of the phone crazies, who still attack non-phoners on sight.
Crossing into New Hampshire, they arrive at the Gaiten Academy, a prep school with one remaining teacher, Charles Ardai, and one surviving pupil, Jordan. The two of them show the newcomers where the local phoner flock goes at night: packing its components into the Academy's soccer field like sardines, "switched off" until morning. They also notice that there are many radios and speakers throughout the field, playing random songs each time. Ardai demonstrates that the phoners have become a hive mind, and are developing psychic and telekinetic abilities. The five of them decide that they must destroy the flock before its powers grow even stronger. They do this by parking two propane tankers on the soccer field and waiting for the flock to settle in for the night. They then blow up the vehicles with a shot from a revolver, killing the flock.
Clay tries to get everyone to flee the resulting scene of carnage, but Ardai is too elderly to travel, and the others refuse to leave him, especially Jordan. The sleep that follows is filled with a horrific dream, in which everyone sees themselves in a stadium, surrounded by hundreds of phoners who broadcast a grim telepathic threat in Latin. A disheveled man wearing a Harvard University hooded sweatshirt approaches, bringing their death. Waking, the heroes compare notes and dub him "The Raggedy Man". A new flock surrounds their residence, and the trapped normies face the flock's metaphorical spokesman: the man wearing the Harvard hoodie. The flock commits bloody reprisal on all other normals in the area, and orders the protagonists to head north to a spot in Maine called "Kashwak", where there is no cell phone reception. To pre-empt one objection, the flock psychically compels Ardai to commit suicide after writing the word "insane" in multiple languages. Clay and the others bury him and travel north, mostly because Clay is still determined to go home.
En route, they learn that as "flock-killers" they have been psychically marked as untouchables, to be shunned by other normies. They also learn the phoners have recruited normals to guard them while they "sleep". Following a petty squabble on the road, Alice is tragically killed by a loutish pair of normals. After burying her, the group arrives in Clay's hometown of Kent Pond. They discover notes from Johnny which tell them that Sharon turned into a phoner, but that her son survived for several days, before he and the other local normies were prompted by the phoners to head to Kashwak. Clay has another nightmare which reveals that once there, they were all exposed to the Pulse by the phoners. He is still intent on finding his son, but after meeting another group of flock-killers, Tom and Jordan plan to head west to avoid the ceremonial executions the phoners clearly have planned for them. Before leaving, the group discovers that Alice's murderers were compelled into suicide as punishment for touching Alice, an untouchable.
Clay sets off alone, but the others soon reappear driving a small school bus; the phoners have used their ever-increasing powers to force them to rejoin him. One of the other flock-killers, a construction worker named Ray, secretly gives Clay a cell phone and a phone number, telling him to use them when the time is right. Ray then commits suicide. The group arrives at Kashwak, the site of a half-assembled county fair. The travelers notice that the phoners are beginning to behave erratically and are breaking out of the flock. Jordan theorizes that a computer program was the source of the Pulse, and while it is still broadcasting its signal into the battery-powered cell phone network, it has become corrupted with a computer worm that has infected the newer phoners with a mutated version of the original Pulse. Nevertheless, an entire army of phoners is waiting for the flock-killers; among them is Sharon, whom Clay pushes aside. As night falls, the phoners lock the group in the fair's exhibition hall.
As a sleepless Clay waits for his execution the next morning, he discovers what Ray planned with the cell phone: he filled the rear of the bus with explosives, wired a phone-triggered detonator to them, and killed himself to prevent the phoners from telepathically discovering his plan. After Clay informs the group of the plan, they break a window for Jordan to squeeze through so he can drive the bus. He drives the vehicle into the midst of the inert phoners. Thanks to a jerry-rigged cellphone patch set up by the fair workers pre-Pulse, the explosion works exactly as hoped, and another scene of mass carnage rains down. The Raggedy Man and his flock are destroyed.
The majority of the group heads north into Canada, to get out of cellphone coverage and let the approaching winter wipe out the region's unprotected phoners. Clay still seeks his son; after making arrangements with the others for a later rendezvous, he heads south. He searches a town called Gurleyville where surviving phoners wander around, now without a flock mind, utterly disoriented. Some have begun to regain speech and somewhat normal actions but are still insane. He finds Johnny, who received a "corrupted" dose of the Pulse; not only did he successfully wander away from Kashwak, he seems to almost recognize his father. However, Johnny is an erratic shadow of his former self, and so, following a theory of Jordan's, Clay gives Johnny another blast from the Pulse, hoping that the increasingly corrupted iterations of the Pulse will destroy each other and reset his son's brain to normal. The book ends with Clay putting a cell-phone to his son's ear, repeating what he would say to Johnny in pre-Pulse days when there was a phone call; "Fo-fo-you-you." (thanks to Wikipedia)