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'. From 2005 he has contributed a cartoon for The Guardian's Weekend magazine every Saturday. He is represented in Paris by the by Yvon Lambert Gallery, and in 2005 designed a London Underground leaflet cover.
David Shrigley co-directed an animate!-commissioned film with award-winning director Chris Shepherd called Who I Am And What I Want, based on Shrigley's book of the same title. Kevin Eldon voiced its main character, Pete. He also produced a series of drawings and t-shirt designs for the 2006 Triptych festival, a Scottish music festival lasting for three to four days in three cities. He has also designed twelve different covers for Deerhoof's 2007 record, Friend Opportunity.
The name of Jason Mraz's third studio album We Sing. We Dance. We Steal Things. is a reference to a piece of art by Shrigley which caught Mraz's attention while he was travelling through Scotland