Awarded since 1965 by The Guardian, this prize is the oldest and best-established award sponsored by a newspaper. Known until 1999 as The Guardian Fiction Prize, it is now no longer restricted to fiction. Uniquely among book awards, it is open to writing across all genres and judged by both a celebrity panel chaired by the Literary Editor of the Guardian and members of the public who participate through reading groups run by Waterstone's stores. The prize itself amounts to £10,000.

Recent winners include Zadie Smith's White Teeth (2000), Chris Ware's Jimmy Corrigan, or the Smartest Kid on Earth (2001), Jonathan Safran Foer's Everything Is Illuminated (2002), Robert MacFarlane's Mountains of the Mind (2003), Armand Marie Leroi's Mutants: On the Form, Varieties and Errors of the Human Body (2004), Alexander Master's Stuart: A Life Backwards (2005), and Yiyun Li's A Thousand Years of Good Prayers (2006).

The Guardian First Book Award is currently run in association with Waterstone's.