Leon Trout has been a ghost for a million years. His unique position allows him to chronicle the survival and evolution of the human race. In 1986, a pandemic causes all female humans to become infertile, and the species only survives because ten people become stranded on one of the Galapagos Islands away from the disease. Mary Hepburn, a widowed biology teacher, artificially inseminates the fertile females with the sperm of her lover, Captain Adolf von Kleist. For a million years, the offspring of the colonists are the only human survivors on the planet, and they evolve to fit their environment, with fur, flippers, and small brains for swimming and catching fish. Humanity has finally found paradise.

As the novel begins, passengers are waiting at the Hotel El Dorado for "the Nature Cruise of the Century", a round trip to the Galapagos Islands from Ecuador on the new cruise ship Bahía de Darwin. The prospective passengers are James Wait, a con artist traveling under the name Willard Flemming, Mary Hepburn, a recently widowed former biology teacher, wealthy financier Andrew MacIntosh and his blind daughter Selena, computer genius Zenji Hiroguchi, and his pregnant wife Hisako. The other passengers never make it to Ecuador. The cruise is canceled due to a worldwide economic collapse.

Zenji and MacIntosh are both shot by a mentally imbalanced soldier, who accidentally lets six orphan native Kanka-bono girls into the guarded hotel. Starving people storm the Hotel El Dorado and the cruise ship to loot whatever food and goods they have. The passengers and Kanka-bono girls are led out in a bus, driven by the hotel manager Siegfried von Kleist. During the escape, James Wait, a.k.a. Willard Flemming, has a heart attack. Siegfried tries to drive to the hospital, but a bomb hits the city. Peru is attacking Ecuador. The bus makes its way to the port, where the Bahía de Darwin is docked. The passengers get aboard the ship, joining its captain, Adolf von Kleist, Siegfried's brother. Another bomb hits the bay, and the resulting tidal wave drowns Siegfried, who is already showing signs of a congenital mental illness.

Adolf starts the ship, hoping to head for safer shores, but they are lost at sea. James Wait/Willard Flemming convinces Mary to marry him, with the captain presiding, and then he dies. Mary never knows that he was a con man. Finally, the ship runs aground at Santa Rosalia, the northernmost Galapagos Island. At first, the passengers await rescue, but a disease has devastated the population of Earth by causing all women to be infertile. The people pair off into couples. Selena and Hisako become a couple and raise Hisako's baby girl, Akiko, who is born covered in fur. Adolf and Mary live together for ten years, until Adolf learns that Mary has, without his permission, used his sperm to impregnate the six Kanka-bono girls. The resulting colony on Santa Rosalia is populated with the only surviving humans on the planet.

A million years in the future, human beings have evolved into swimming mammals, covered in fur, with small brains and flippers instead of hands. The narrator, Leon Trout, is the ghost of a welder who was killed during the construction of the Bahía de Darwin. Instead of entering the afterlife, he's been stranded on Earth as a ghost because of his curiosity about the human condition. He portrays the evolved humans, who don't use tools, build buildings, or have big dreams, as a kind of paradise. All human violence and pollution is gone. Leon is waiting for the blue tunnel to appear again and lead him to the afterlife. There's nothing left about the human condition for him to explore, and he's ready to go.