Born in Frome, Somerset, Higson was educated at Sevenoaks School, Kent and at the University of East Anglia in Norwich (where his brother taught from 1986 to 2008, latterly as Professor of Film Studies) where he met Paul Whitehouse, David Cummings and Terry Edwards. Higson, Cummings and Edwards formed the band The Higsons of which Higson was the lead singer from 1980 to 1986. They released two singles on the Specials' 2 Tone Records label. This was after he had formed the punk band The Right Hand Lovers, wherein he performed as "Switch". Higson then became a decorator – including decorating the house of Stephen Fry and Hugh Laurie – before he turned to writing for Harry Enfield with Paul Whitehouse and performing comedy. He came to public attention as one of the main Writers and performers of the BBC Two Sketch show The Fast Show (1994–2000). He worked with Whitehouse on the radio comedy Down the Line and is to work with him again on a television project, designed to be a spoof of Celebrity travel programmes.

Higson published many novels through the early to mid-1990s which take a slightly dystopian look at everyday life and have a considerably more adult tone than his other work, with characters on the margins of society finding themselves spiralling out of control. This has led Time Out to describe him as "The missing link between Dick Emery and Bret Easton Ellis".

In 1994 Higson co-wrote (with Lise Mayer) the screenplay for the film thriller Suite 16.

He worked as Producer, Writer, Director and occasional guest star on Randall & Hopkirk from 2000 to 2001. Subsequent television work has included writing and starring in BBC Three's Fast Show spin-off sitcom Swiss Toni. He has starred in Tittybangbang on BBC Three and appeared as a panellist on QI. In 2010 he co-directed and starred in the series Bellamy's People.

In 2004, it was announced that Higson would pen the Young Bond series of James Bond novels, aimed at younger readers and concentrating on the character's school-days at Eton. Higson was himself educated at Sevenoaks School, where he was a contemporary of Jonathan Evans, former Director General of MI5. The first novel, SilverFin, was released on 3 March 2005 in the UK and on 27 April 2005 in the US. A second novel, Blood Fever, was released on 5 January 2006 in the UK and 1 June in the US. The third novel, Double or Die, was published on 4 January 2007 having had its title announced the day before. The next, Hurricane Gold, came out in hardcover in the UK in September 2007. In this year he also made a debut performance on the panel show QI. His final Young Bond novel, By Royal Command, was released in hardcover in the UK on 4 September 2008.

In 2011, Higson appeared with the original cast (with the exception of Mark Williams) in an online-only version of The Fast Show sponsored by Foster's Lager.

In June 2013 Higson wrote a television adaptation of A Caribbean Mystery, the story that inspired Ian Fleming to give the protagonist of his novel "Casino Royale" a name. He also portrayed the ornithologist James Bond in the production.

In 2015 Higson adapted the novel Strange Case of Dr Jekyll and Mr Hyde by Robert Louis Stevenson for ITV Studios into a ten part adventure series set in the 1930s titled Jekyll and Hyde.

In 2018 Higson wrote a Fighting Fantasy gamebook entitled The Gates Of Death, which was published by Scholastic books as part of their campaign to relaunch the Fighting Fantasy franchise. He is a long term FF enthusiast, having attended Fighting Fantasy Fest 2 in London the previous year and also made a cameo appearance in the Ian Livingstone gamebook Blood Of The Zombies.