Locke began work in 1986 illustrating Deadworld, a zombie horror comic that soon became an underground hit.
Since then, his illustrative talents in comics have included The Sandman, American Freak, Batman, Witchcraft: Le Terreur, The Spectre, and A History of Violence, which was later made into a movie directed by David Cronenberg and starring Viggo Mortensen. He has done work for 2000 AD, including one Judge Dredd story.
Locke has also created ultra-violent watercolor paintings to be used as album covers for the death metal band Cannibal Corpse. Also, he has provided illustrations for the "weird erotica" of dark-fantasy author Caitlín R. Kiernan, providing black and white artwork strongly reminiscent of Aubrey Beardsley's style for her collections Frog Toes and Tentacles and Tales from the Woeful Platypus, as well as for Kiernan's monthly Sirenia Digest. Recent projects have included illustrating the first issue of Polluto: The Anti-Pop Culture Journal. He is also known for providing art work for RPGs by White Wolf Publishing and Wizards of the Coast. A press release dated May 6, 2012 announced Locke's graphic novel collaboration with writer Jasmine Lyraka for the Wagnerian opera metal project Lyraka.

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