Dufresne's first novel, Louisiana Power and Light (1994)

was named a [[New York Times]] notable books of the year, as was his second novel, ''Love Warps the Mind a Little'' (1997).

Dufresne's third novel, Deep in the Shade of Paradise (2002) was a Book Sense Top Ten of the Year selection. It contains some of the same characters as Louisiana Power and Light, although in an interview with writer Max Ruback which appeared in the Winter 2001 issue of the literary magazine, Turnrow Dufresne has said that he does not consider it to be a sequel. Both of these novels developed from a long short story in his first collection, The Way that Water Enters Stone(1991).

Dufresne published a second short story collection, Johnny Too Bad in 2005. The title story had previously been chosen for compilation in New Stories from the South: The Year's Best, 2003. In 2003, he also published The Lie That Tells a Truth: A Guide to Writing Fiction.

Dufresne published a fourth novel, Requiem, Mass. in 2008.

All of the named books were published originally by W. W. Norton, which has kept them in print, except for the first book of short stories, The Way that Water Enters Stone. Plume, an imprint of Dutton-Signet, a division of Penguin Books republished that book as a trade paperback in 1997, but it is also out of print. Plume also published still-in-print trade paperback editions of Louisiana Power and Light(1995), Love Warps the Mind A Little (1998) and Deep in the Shade of Paradise (2003).

In 1998, Dufresne collaborated with Carl Hiaasen, Dave Barry, Elmore Leonard and nine other South Florida writers on Naked Came the Manatee, a detective novel published by Ballantine Books, a division of Random House. []

Dufresne's short story "This is the Age of Beautiful Death" appears in Blackbird: an online journal of literature and the arts.

His screenplay, Freezer Jesus, based on another story in his first short story collection, won the 2002 screenwriting contest and was produced that year by the Grand Valley State University Summer Film Project. The cinematographer, Jack Anderson, has a long list of Hollywood credits. After being selected for several other festivals, it was featured at Saugatuck, Michigan's 2006 Waterfront Film Festival.

His play, Trailerville premiered at The Blue Heron Theatre off-off-broadway in 2005.[3]

In the Summer of 2007, Grand Valley State University produced another film for which Dufresne is the screenwriter, To Live and Die In Dixie. The cinematographer is Jack Anderson and the film director is Harper Philbin. The film was released in 2008. [4][5]