Oryx and Crake opens with a man named Snowman waking up in a tree. Some kind of catastrophic event has taken place, but the reader does not yet know what the event was or what caused the event. It appears that Snowman may be the sole survivor of the event, aside from a group of childlike people he refers to as the “Children of Crake,” who walk around naked and clearly have a unique genetic composition.

The post-apocalyptic world represents the novel’s present time, and each chapter of the book moves back and forth between Snowman’s present experiences and his memories of his pre-apocalypse life, when he went by the name Jimmy. These separate but connected narrative threads weave together as the book moves along.

In the present-time narrative, Snowman watches over the Children of Crake, or the “Crakers,” to whom he feels a sense of responsibility. Snowman spins fictional stories about individuals named Crake and Oryx, whom the Crakers understand as kinds of gods: whereas Crake watches over the Crakers, Oryx presides over the lives and well-being of plants and animals.

Though the Crakers appear well adapted to the post-apocalyptic environment, Snowman struggles to keep himself fed and hydrated. He knows where he can find more much-needed supplies, but the location is far away, and he’s never left the Crakers for more than a day. Nevertheless, he decides to make the dangerous journey. After informing the Crakers, he sets off for the Paradice facility in the RejoovenEsense Compound, where he once worked alongside Crake.

On his journey to Paradice, Snowman encounters several threats, including a herd of cunning and dangerous genetically engineered animals called pigoons. Though Snowman is slowed down by an infected foot wound, he eventually reaches Paradice, where he gathers crucial supplies. With his booty in tow, he limps back to the Crakers.

Although Snowman’s narrative functions as a frame for the novel, the majority of the book focuses on Snowman’s memories of his prior self, Jimmy. This narrative begins with Jimmy’s boyhood. His parents worked at a company called OrganInc Farms, which researched ways to grow human organs cheaply and effectively. Jimmy’s mother grew increasingly disgusted by the company’s work, which caused friction with her husband. She suffered a long period of depression, and soon after her husband got a high-status new job, she ran away, abandoning Jimmy.

Jimmy suffered greatly after his mother’s disappearance. However, he survived through a blossoming friendship with a new student at HelthWyzer High named Crake, with whom he spent a lot of time watching graphic videos of sex and violence on the internet. Whereas Jimmy lacked an aptitude for math and science, Crake proved himself gifted in both disciplines. After they graduated, Crake went off to the prestigious Watson-Crick Institute, where he majored in bioengineering. He graduated early and soon began to lead his own research projects.

Meanwhile, Jimmy attended a lower-tier school specializing in the arts and humanities. There he majored in a program called Problematics, which prepared him for a career in advertising. After graduating, Jimmy started working for a company called AnooYoo, where he applied his dissertation research on twentieth-century self-help manuals to marketing campaigns for self-improvement products. Although Crake and Jimmy kept up with and occasionally visited each other, their communications dwindled as the years progressed.

Occasionally during his years at AnooYoo, employees of an agency called the CorpSeCorps came to Jimmy’s apartment to interrogate him about his mother’s whereabouts, but Jimmy had long since lost contact with her. In his fifth year at AnooYoo, the agents came again and showed Jimmy a video of his mother’s execution. The news of his mother’s death sent Jimmy into a profound depression, which only came to an end when Crake showed up at his apartment and asked Jimmy to come work with him at RejoovenEsense. Jimmy accepted the job, which involved running an ad campaign for a new pill called BlyssPluss that Crake had designed to improve users’ libido while simultaneously (and secretly) making them unable to have children. Crake presided over an additional top-secret project located in a special facility called Paradice, which housed a new breed of genetically engineered humans: the Crakers.

At Paradice, Jimmy met a woman named Oryx, whom Crake had hired to teach the Crakers and to help distribute the BlyssPluss pills worldwide. Jimmy recognized Oryx from a child pornography video that he and Crake had seen when they were teenagers. Crake had met Oryx in person when he was in college and employed her for sex work. Oryx and Crake developed a relationship, and when Crake started at RejoovenEsense, he hired Oryx to work there too. Oryx seduced Jimmy, and Jimmy worried that Crake would feel jealous if he found out. One night, when Crake was away from the facility and Oryx was picking up takeout, news reports started coming in about simultaneous plague outbreaks unfolding around the world. Oryx called Jimmy to explain that the BlyssPluss pills contained a delayed-release contagion, and that she had unwittingly participated in the outbreak. Crake’s plague spread quickly and killed the majority of people on the planet.

In the first hours of the outbreak, Crake returned to Paradice with Oryx in tow, and he slit her throat in front of Jimmy. Jimmy then shot Crake. For the first few weeks after the outbreak, Jimmy remained locked in the Paradice facility alone, searching for reasons that Crake would kill Oryx. Eventually, he introduced himself to the Crakers as “Snowman” and led them to a new home near the ocean, where they still live in the novel’s present time.

The novel ends with Snowman’s present-time journey from Paradice back to the Crakers. When he arrives, the Crakers inform him that they saw a group of people like him in the area. Snowman tracks down the other humans and wonders whether to approach them as friends or foes.