The novel is split into two storylines. The first follows Snowman’s endeavors after the human population of Earth has been wiped out by a massive deadly plague, when all that apparently remains are the Crakers (a genetically manipulated group of beings who are similar to but not the same as humans and survive easily in this environment) and Snowman himself, who watches over the Crakers and struggles himself to survive. The second storyline follows Jimmy (this was Snowman’s name before the plague hit) and describes how the Crakers, the plague, and Snowman’s lonely existence came to be.
The novel opens with Snowman going through his daily routine. He eats some of the food he’s scavenged and stored, hears voices from the past in his head, and interacts with the Crakers, who ask him to tell stories from the past. Snowman invents for them a mythology in which someone called Crake is their creator and god, and Oryx, a mysterious woman who appears to Snowman’s hallucinating mind in his loneliest moments, is their caregiver and creator of all animal life.
Through flashbacks we learn of Jimmy’s childhood. He grew up inside a “Compound”—a community built around a corporation where rich scientists and their families live. The compounds are cordoned off from an outer world called the “pleeblands,” where everyone who is not employed by a corporation must live. Jimmy’s father and mother (Sharon) fight incessantly. His mother used to work for the corporations like his father does, but she quits in disgust at corporate corruption and greed and experimentation on animals. Eventually she leaves, taking Jimmy’s beloved pet Killer with her (Killer is a genetic combination of a skunk with a raccoon called a “rakunk”). She explains in a note that her conscience could bear it no longer. Jimmy’s father continues to live with Jimmy in the compounds, and he invites a coworker, Ramona, with whom he has been having at least an emotional affair for many years, to move in.
Jimmy’s only childhood friend is Crake, who is a scientifically gifted young man with a mysterious air, who find Jimmy’s aversion to science (Jimmy is a “words person” not a “numbers person”) fascinating. The two spend many hours playing computer games and watching pornographic or violent video on Crake’s stepfather’s (called Uncle Pete) computer server. One game they play is called Extinctathon, and involves cataloguing the long list of extinct species. Crake takes his name from the extinct “Red-Necked Crake.” One day when they are watching child pornography, Jimmy sees a young girl who catches his attention—he believes this girl grows up to be Oryx.
Jimmy and Crake go to separate colleges—Crake to a prestigious school for the sciences, and Jimmy to a dilapidated humanities school, where he studies rhetoric and advertising strategies. When Jimmy graduates he obtains a job writing pamphlets for a corporation called AnooYoo—he is bored and depressed by this work and begins drinking heavily and develops a sex addiction. On the news one day he sees a story about a sex scandal in San Francisco, where several girls were being kept in the garages of wealthy men. He sees Oryx among the girls, giving an interview. During this time he is also informed of the death of his mother, who has been executed by compound security forces for treason. One day Crake appears and invites him to go bar crawling in the pleeblands. Before they go Crake gives Jimmy an injection to protect him from diseases that exist there. While they are out Crake tells Jimmy about a job at the prestigious RejoovenEsense compound, where Crake is a higher-up. Jimmy agrees to take the job.
We learn that Snowman must now make his way back to this RejoovenEsense compound, because he knows there will be weapons, food, and other supplies there and he is starving to death and has no protection from predators. He tells the Crakers he must leave to go see Crake, and they express concern about his safety on this long journey. Snowman tells them he must go alone, and leaves with what supplies he has left. He is increasingly troubled by voices from his past and visions of Oryx, whom he loved dearly. His journey is difficult—he is hunted by pigoons (a genetically modified species of pig with human organs and brain tissue.) On one night of his three-day journey he cuts his foot on a shard of glass and must nurse a growing infection. He eventually makes it to the RejoovenEsense compound and goes to a dome at the center of it called Paradice.
We lean via more flashbacks that Paradice is Crake’s project, and the project to which Jimmy is assigned when he arrives at RejoovenEsense. Crake is working on a two-part initiative to eliminate human suffering. The first is a pill called BlyssPluss, which increases libido and energy to eliminate sexual frustration. It is being tested on poor sex workers with positive results. The pill also contains an undisclosed contraceptive—everyone who takes it becomes unknowingly sterilized—in order to reduce overpopulation, which Crake believes is the foremost cause of human suffering. The second part is a project involving the manipulation of human embryos. Crake shows Jimmy the results of this effort, a group of genetically modified humans called the Crakers. They are perfect, strikingly beautiful creatures with bright green eyes. They have plant and animal traits bred into them to make them sturdy and to ensure that they reproduce infrequently and experience no lust, attachment, or sexual frustration. Crake has also tried to breed religion, art, and philosophy out of them (though we know from Snowman’s eventual interactions with the Crakers that this has more or less failed).
One of Crake’s employees is a beautiful woman named Oryx whom Jimmy recognizes from the earlier videos he has seen of her. She is a caretaker for the Crakers, and teaches them how to make fire and eat. She also distributes BlyssPluss pills to test subjects in whorehouses and sex clinics all over the world. Though Oryx and Crake have a sexual relationship, and Jimmy can see that Crake loves Oryx, Oryx feels no emotional attachment to Crake and begins having an affair with Jimmy. Jimmy learns all about her past (she has worked in various sex trades) and falls deeply in love with her. He worries often that Crake knows of the affair, but Oryx insists Crake doesn’t believe in jealousy and has too elegant a mind for such things. She ominously mentions once or twice that Jimmy must promise to take care of the Crakers, should anything ever happen to her. One day Oryx goes out for pizza and doesn’t come back. Jimmy hears that a terrible plague is raging across every continent. He receives a phone call from Oryx, who is crying and apologizing: the plague had been in the BlyssPluss pills that Oryx had been distributing, and she had no idea. Jimmy begins to realize what has happened. He is safe in the air-locked Paradice dome, but must kill the other employees because he believes they will panic and put him in danger. Crake appears outside the dome and demands Jimmy let that Jimmy let him in. Jimmy hesitatingly unlocks the door, and Crake explains that Jimmy has been immunized by the injection he received to go into the pleeblands. Crake has Oryx, unconscious, draped over his arm. He tells Jimmy he must take care of the Crakers, and slits Oryx’s throat. In shock and horror, Jimmy shoots Crake. Jimmy waits in the dome for weeks, and watches the plague wipe out most of humanity. When the time comes, he leads the Crakers out of Paradice to the seashore where they now live. He hates Crake, and resents fulfilling his diabolical plan, but cannot stand to abandon the Crakers.
Snowman steps over the remains of Oryx and Crake as he goes into the Paradice dome. He gathers the supplies he needs, and does his best to treat the growing infection in his foot. He journeys back to the Crakers, who are delighted to see him. They also tell him that they have seen other men who look like Snowman. Snowman is shocked and elated to hear this, and the next morning travels along the shore to find these people. He sees three—two men and one woman—sitting around a fire on the beach. He wonders what will happen if he goes to talk to them—will they be friendly, will they attack him? Will they kill him? Will he kill them? The book ends here, remaining ambiguous about what he decides to do.