Initially a freelance music journalist (using both his own name and the pseudonym "Audrey Witherspoon"), Weatherall's first studio work was alongside DJ Paul Oakenfold on the Club remix of "Hallelujah" for the Happy Mondays. Other remixes followed, including "World in Motion" by New Order and "Loaded", a hit remix of Primal Scream's earlier track "I'm Losing More Than I'll Ever Have". He joined fellow scenesters Terry Farley and Pete Heller to form Boy's Own, initially a magazine commenting on football, fashion, records, etc. They also did parties, and had a record label under the name of Boys Own Recordings (which went on to be called Junior Boy's Own in 1992 upon Weatherall's departure). Along with engineer Hugo Nicholson and singer Anna Haigh, they released two singles as Bocca Juniors on Boys Own Records, "Raise (53 Steps to Heaven)" and "Substance".
He formed the electronic music trio The Sabres of Paradise in 1993. He has promoted the Bloodsugar and Sabresonic club nights. In early 1996, after shutting down Sabresonic, Weatherall and Keith Tenniswood became Two Lone Swordsmen, signing to Warp Records label and setting up Rotters Golf Club for their own dancefloor-orientated work.
Weatherall has cited humour as an important component in his musical ideology.
He has produced such artists as Beth Orton, Primal Scream and One Dove, and has remixed the work of Björk, Siouxsie Sioux, The Orb, The Future Sound of London, New Order, Manic Street Preachers, My Bloody Valentine, Saint Etienne, James and many others.
In late 2006, he released his debut solo single "The Bullet Catcher's Apprentice", followed by his debut solo album "A Pox On The Pioneers" in 2009. Both were released on his Rotters Golf Club imprint.
In late 2007 and early 2008, a song entitled "Feathers" by Weatherall was used in an advert for a Volkswagen Tiguan, while in 2009 the Two Lone Swordsmen track "Shack 54" was used on a new version of a previous year's Ford Fiesta advert.