The book received mostly favourable reviews in the press. The Globe and Mail, Maclean's, and The Toronto Star ranked the novel high among Atwood's works and Helen Brown, for the Daily Telegraph, wrote "The bioengineered apocalypse she imagines is impeccably researched and sickeningly possible: a direct consequence of short-term science outstripping long-term responsibility. And just like the post-nuclear totalitarian vision of The Handmaid's Tale, this story is set in a society readers will recognise as only a few steps ahead of our own." For The New Yorker, Lorrie Moore called the novel "towering and intrepid". Moore wrote, "Tonally, 'Oryx and Crake' is a roller-coaster ride. The book proceeds from terrifying grimness, through lonely mournfulness, until, midway, a morbid silliness begins sporadically to assert itself, like someone, exhausted by bad news, hysterically succumbing to giggles at a funeral." Joyce Carol Oates noted that the novel is "more ambitious and darkly prophetic" than The Handmaid's Tale. Oates called the work an "ambitiously concerned, skillfully executed performance".
Joan Smith, writing for The Observer, faulted the novel's uneven construction and lack of emotional depth. She concluded: "In the end, Oryx and Crake is a parable, an imaginative text for the anti-globalisation movement that does not quite work as a novel."
In a review of The Year of the Flood, Ursula K. Le Guin defended the novel against criticism of its characters by suggesting the novel experiments with components of morality plays.