John (whose last name is never given) tells readers he began writing a book thousands of cigarettes, numerous bottles of booze and two wives ago. He planned to call it The Day the World Ended and to focus on the day the first atomic bomb was dropped. John’s book actually becomes another story entirely. His tale begins as he researches the deceased Dr. Felix Hoenikker, the scientist known as the father of the atomic bomb. He writes to the doctor’s youngest son, Newt, whom he later learns is an artist, a pre-med flunkee and a small person. Newt responds in a candid letter about the man who single-handedly raised him and his two siblings, Frank and Angela. Newt’s account highlights the doctor’s self-absorption, indifference and ignorance to the danger he brought into the world and sets the stage for the book’s critique of modern man.
John visits Dr. Hoenikker’s hometown and his former supervisor, Dr. Breed. He learns more about Dr. Hoenikker’s obsession with his scientific tinkerings and his neglect of all human beings, including his family. Dr. Breed tells John about a hypothetical substance called ice-nine with which Dr. Hoenikker was tinkering at the time of his death. In theory, ice-nine would stack atoms in such a way as to freeze any water it touched with a melting point of 114.4 degrees. While Breed insists the substance never really existed, John learns much later that the doctor had actually created it. Upon his death, his three children secretly divided the remaining shards of ice-nine among themselves.
John learns that Newt’s older brother, Frank, is the Minister of Science and Progress on a small, remote island called San Lorenzo. John wonders how the troubled Frank landed such a position and decides to visit him. The nation has a colorful history. Though many countries have ruled it at various times, no one fought for it when another country took over. The natives live in extreme poverty, ruled by a dictator called “Papa” Monzano. “Papa” has a hauntingly beautiful daughter named Mona, and John falls for her the moment he sees her picture in the San Lorenzo guidebook.
En route to San Lorenzo, John also reads about the country’s rogue spiritual leader called Bokonon. The Books of Bokonon contain the prophet’s writings in the form of short rhymes, calypso songs and re-tooled famous quotes and biblical principles. Bokonon makes it clear that his book is made up entirely of lies, yet nearly all San Lorenzo residents follow him. John learns that some years earlier, two men named McCabe and Johnson washed ashore on San Lorenzo and decided to rule it. They determined that since they couldn’t improve the economic situation to make the people less miserable, they would use religion to give the people hope. They further believed that if religion were outlawed, people would become all the more passionate about following it. So Johnson became Bokonon and created his own religion. McCabe ruled the nation with an iron fist, threatening residents with impalement on a giant hook if they were caught following Bokonon. Despite the clearly false, cynical underpinnings of Bokononism, John becomes a follower as well. His newfound beliefs thread throughout the entire novel.
John flies to San Lorenzo with the nation’s new American ambassador and his wife. Also aboard the plane are an American bicycle builder and his wife looking for cheap laborers, and Newt and his sister, Angela. To John’s chagrin, they announce they’ll be attending Frank’s marriage to Mona Monzano. “Papa,” already in poor health, nearly dies at the ceremony to welcome the group. A panicked Frank, who doesn’t have the social skills to rule in his future father-in-law’s stead, begs John to become the next leader of San Lorenzo. He promises to handle the technical details, and even insists John should marry Mona. John reluctantly agrees when Mona becomes part of the package. He meets the beautiful Mona at last, only to discover she is strange and passive. He and Frank go to “Papa” when they learn the end is near. Though “Papa” keeps calling for ice, he will not accept it when it’s given. The men are finally called in to see his strangely stiff dead body, and John realizes the ice “Papa” wanted was ice-nine. “Papa” had used it to kill himself. Frank admits he bought his way into his position in San Lorenzo by telling “Papa” about a powerful substance he possessed. The man giving “Papa” last rites touches the ice-nine to his lips and dies also. John and Dr. Hoenikker’s three children secretly and cautiously clean up the ice-nine mess and hide the bodies. John learns that, like Frank, the other siblings used their ice-nine for selfish gain. The unattractive Angela got herself a trophy husband, who sold the secrets of ice-nine to the U.S. government. Newt got himself a week of passion with a Ukrainian ballerina, who promptly left him and shared ice-nine with Russia.
A ceremony involving the ambassador is already in progress at the castle. John decides to wait until it is completed to tell the others that “Papa” is dead and that he is taking over. At the ceremony, a military plane explodes and hits the castle, causing part to crumble and “Papa’s” body to be thrown into the sea. The water immediately turns to ice-nine, tornados form and the sky darkens. Mona and John run for safety to “Papa’s” underground bunker, where they hole up for several days until they stop hearing tornados outside. When they venture out, they see the ice-nine has caused mass devastation. They come upon a mountain of dead native bodies who, at Bokonon’s suggestion, all killed themselves by tasting ice-nine. Mona feels it’s a simple solution, and she does the same. John finds the bicycle manufacturer, his wife, Newt and Frank alive. They seem to be the only ones left on earth. Just as John wonders what he’s supposed to do, he and Newt see Bokonon on the roadside. Bokonon says if he were a younger man, he would write a book, climb a mountain, ingest some ice-nine and thumb his nose at God as he died. Readers are left to assume that’s what John does.