Shrigley was born in Macclesfield on 17 September 1968, the younger of two children born to Rita (née Bowring) and Joseph Shrigley. He moved with his parents and sister to Oadby, Leicestershire, when he was two years old. He did the Art and Design Foundation course at the Leicester Polytechnic in 1987, and then studied Environmental Art at the Glasgow School of Art from 1988 to 1991.
Although he works in various media, he is best known for his mordantly humorous cartoons released in softcover books or postcard packs.
Like the poet Ivor Cutler, Shrigley finds humour in flat depictions of the inconsequential, the unavailing and the bizarre although he is far fonder of violent or otherwise disquieting subject matter. Shrigley's work has two of the characteristics often encountered in outsider art an odd viewpoint, and (in some of his work) a deliberately limited technique. His freehand line is often weak, which jars with his frequent use of a ruler; his forms are often very crude; and annotations in his drawings are poorly executed and frequently contain crossings-out (In authentic outsider art, the artist has no choice but to produce work in his or her own way, even if that work is unconventional in content and inept in execution. In contrast, it is likely that Shrigley has chosen his style and range of subject matter for comic effect).
As well as authoring several books, he directed the video for Blur's "Good Song" and also for Bonnie 'Prince' Billy's "Agnes, Queen of Sorrow". In 2005 designed a London Underground leaflet cover. Since 2005, he has contributed a cartoon for The Guardian's Weekend magazine every Saturday. Other projects have included the album Worried Noodles (Tom Lab, 2007) where musicians interpret his writings as lyrics, including collaborations by David Byrne, Hot Chip, and Franz Ferdinand.