Anathem received mostly positive reviews. Paul Boutin wrote in The Wall Street Journal that "the lasting satisfaction of Anathem derives … from Mr. Stephenson's wry contempt for today's just-Google-it mindset. His prose is dense, but his worldview contagious." On Salon.com, Andrew Leonard described the book as "a page turner and a philosophical argument, an adventure novel and an extended existential meditation, a physics lesson, sermon and ripping good yarn."
Michael Dirda of The Washington Post disagreed, remarking that "Anathem will certainly be admired for its intelligence, ambition, control and ingenuity", but describing it as "fundamentally unoriginal", "grandiose, overwrought and pretty damn dull." The novel entered The New York Times Best Seller list for Hardcover Fiction at number one  and achieved the rare distinction for a novel of being reviewed in Nature.
Anathem won the Locus Award for Best Science Fiction Novel in 2009  and collected nominations for the Hugo, Arthur C. Clarke, and John W. Campbell Memorial Awards the same year. In 2008, the novel received a nomination for the British Science Fiction Award.