A prose writer in a variety of genres, including Western, horror, science fiction, mystery, and suspense, he has also written comic books and screenplays.

[4] Lansdale's writing is characterized by a deep sense of irony, and features strange or absurd situations or characters, such as Elvis Presley and John F. Kennedy battling a soul-sucking Egyptian mummy in a nursing home (the plot of his Bram Stoker Award-nominated novella, Bubba Ho-Tep, which was made into a movie by Don Coscarelli).

Lansdale depiction of East Texas is essentially "good" but blighted by racism, ignorance, urban and rural deprivation and corrupt public officials.

[9] Much of Lansdale's work has been issued and re-issued as limited editions by Subterranean Press[10] and as trade paperbacks by Vintage Crime/Black Lizard Publications.

[17] Lansdale and daughter Kasey started a new publishing company called Pandi Press to control the re-issue and publication of his older works.

[18] Lansdale book of essays and memoirs, Miracles Ain't What They Used To Be, was released by PM Press's Outspoken Author Series.

He released a book of poetry titled Apache Witch as a limited edition that sold out right away and a Nat Love novella, Radiant Apples, published by Subterranean Press.

The film featured Elvis Presley and a man who believes himself to be John F. Kennedy, confined to an old-age rest home, teaming up to fight a mummy who is stealing their friends' souls.

[35] Backup Media and Memento Films International financed Cold in July, an adaptation of Lansdale's cult novel was directed by Jim Mickle, with acting by Michael C. Hall and Sam Shepard.

[39] Nick Damici and Jim Mickle developed a Hap and Leonard private investigator series for the Sundance Channel, which premiered in March 2016.

[40][41] On June 27, 2016, SundanceTV renewed the series for a six-episode second season, which aired in 2017[needs update] and was based on the second novel, Mucho Mojo.

In the "Long Fiction" category (which is for novellas, though it also initially included comic book work as well), he won in 1989 for On the Far Side of the Cadillac Desert with Dead Folks, 1997 for The Big Blow, and 1999 for Mad Dog Summer (a shared award with Brian A. Hopkins' "Five Days in April").

In 1992 the story The Events Concerning a Nude Fold-Out Found in a Harlequin Romance shared the "Long Fiction" award with Aliens: Tribes by Steve Bissette.

[50] He won a Bram Stoker Award in the long fiction category for Fishing for Dinosaurs[51] which was published in the collection Limbus 2.