The story is told in a nonlinear order and events become clear through flashbacks (or time travel experiences) from the unreliable narrator who describes the stories of Billy Pilgrim, who believes himself to have been in an alien zoo and to have experienced time travel.
Chaplain's Assistant Billy Pilgrim is a disoriented, fatalistic and ill-trained American soldier who refuses to fight ("Billy wouldn't do anything to save himself"). He does not like war and is captured by the Germans during the Battle of the Bulge in 1944. Billy's near death is the consequence of a string of events. Before the Germans capture Billy, he meets Roland Weary, a jingo character and bully, just out of childhood like Billy, who constantly chastises him for his lack of enthusiasm for war. When Weary is captured, the Germans confiscate everything he has, including his boots, giving him hinged, wooden clogs to wear; Weary eventually dies of gangrene caused by the clogs in Luxembourg. While dying in a railcar full of prisoners, Weary manages to convince another soldier, Paul Lazzaro, that Billy is to blame. Lazzaro vows to avenge Weary's death by killing Billy, because revenge is "the sweetest thing in life."
At this moment, Billy becomes "unstuck in time" and he experiences moments from various points in his life. Billy and the other prisoners are transported to Luxembourg. By 1945, the prisoners are transported to Dresden to perform "contract labor". The Germans put Billy and his fellow prisoners in a disused slaughterhouse in Dresden. Their building is known as "Schlachthof-fünf" ("Slaughterhouse Five"). During the bombing, the prisoners of war and German guards hide in a deep cellar. Because of their hiding place, they are some of the few survivors of the firestorm caused by Allied bombing between 13 and 15 February 1945. After the war in May 1945, he is transported from Germany to the United States, receiving an honorable discharge from service in July 1945.
A few months after the war ends, Billy is institutionalized with post-traumatic stress disorder and put into psychiatric care to recover. A man named Eliot Rosewater introduces Billy to the novels of an obscure science fiction author named Kilgore Trout. Once Billy is released, he marries Valencia Merble. Valencia's father owns the Ilium School of Optometry, which Billy later attends. In 1947, Billy and Valencia's first child Robert is born and two years later they have a daughter named Barbara. On Barbara's wedding night, Billy is captured by an alien space ship and taken to a planet billions of miles away from Earth called Tralfamadore. The Tralfamadorians are described as being able to see in four dimensions, allowing them to simultaneously observe any and every point in the space-time continuum. They universally adopt a fatalistic worldview. The book adopts the Tralfamadorian philosophy on death, dispassionately saying "so it goes" whenever it refers to someone's demise.
On Tralfamadore, Billy is put in a transparent geodesic dome exhibit in a zoo that mimics a house on Earth. The Tralfamadorians later abduct a porn star named Montana Wildhack, who disappeared and is believed to have drowned herself in the Pacific Ocean, with the intention of seeing the two mate. She and Billy fall in love and have a child together. Billy is instantaneously sent back to Earth in a time warp to relive past or future moments of his life.
In 1968, Billy and a copilot are the only survivors of a plane crash. Valencia dies of carbon monoxide poisoning while driving to the hospital where Billy is being treated. Billy shares a hospital room with Bertram Rumfoord, a Harvard history professor. Billy eventually talks about the bombing of Dresden and the professor claims it was justified.
Billy's daughter takes him home to Ilium. He sneaks out and drives to New York City and checks in to a hotel. That evening he wanders around Times Square and visits a book store featuring pornography. Billy sees some Kilgore Trout books and reads them. That night he goes on a radio show where he starts talking about his time-travels to Tralfamadore and is kicked out of the studio. He returns to his hotel room, falls asleep and time-travels back to 1945 Dresden where the book ends.