[6] His early work appeared in the pages of Heavy Metal, Epic Illustrated, Bizarre Adventures, Scholastic Corporation's Weird Worlds and Bananas illustrating stories written by Goosebumps founder and author R. L. Stine, and he worked with Rick Veitch on the graphic novelization of Steven Spielberg's motion picture 1941.

[3] Bissette is best known for his multiple award-winning collaboration with writer Alan Moore and inker John Totleben on DC Comics' Saga of the Swamp Thing (1983–1987).

[7] Under the company name of Spiderbaby Grafix, he later published the horror anthology Taboo, the original home of Moore and Eddie Campbell's From Hell, and Tim Lucas' Throat Sprockets, illustrated by Mike Hoffman and David Lloyd.

Bissette subsequently worked with Moore, Totleben, and Rick Veitch on the Image Comics' limited series 1963, their final creative collaborative effort.

"[16] He teaches courses in Comic Art History, Drawing, and Film at the Center for Cartoon Studies in White River Junction, Vermont Since 2005, Bissette has also edited and published Green Mountain Cinema, a trade paperback journal devoted to the independent cinema scene in his home state of Vermont,[8] as well as five volumes of Blur, collecting his film reviews and criticism.

[22] His work with Alan Moore and John Totleben earned a nomination for the 1985 "Best Single Issue" Jack Kirby Award for Swamp Thing #34.