Little was born one month after his mother attended the world premiere of Psycho. He published his first novel, The Revelation, with St. Martin's Press in 1990. After reading it, Stephen King became a vocal fan of Little's work, and Little won the Bram Stoker Award for "Best First Novel" in 1990. He moved to New American Library for his next two novels, but was dropped from the company after he refused to write a police procedural as his next novel. He eventually returned to New American Library, with whom he continues to publish his novels.
Little has stated on several occasions that he considers himself a horror novelist, and that he writes in the horror genre, not the "suspense" or "dark fantasy" genres. He is an unabashed supporter of horror fiction and has been described as a disciple of Stephen King.
Little has stated in the past that he does not like computers, and refuses to operate an official web site.
Recurring themes in Bentley Little's work include distrust of conformity (The Association, The Ignored), distaste for large corporations (The Store, The Policy), and taboo subjects such as incest. These elements, particularly the latter, strongly recall the work of J.G. Ballard. Little's novels tend to contain overtly supernatural forces rather than relying on pseudo-scientific explanations like many other horror stories. Nearly all of his novels have extremely simple titles.
There is a recurring character in several of Little's novels, a horror author named Phillip Emmons, after a pseudonym Little used for an early novel. A somewhat bumbling FBI agent named Greg Rossiter also appears in supporting roles in several books, as do references to a company called Automated Interface, which is mentioned in The Ignored, The House, His Father's Son, and The Return and plays a larger role in The Ignored. In addition, one of the main characters of Dominion, Penelope Daneam, is mentioned in The Return as having been a love interest of one of that book's characters when he was in college, and the Mogollon Monster from The Return is mentioned briefly in The Summoning.
The Store is mentioned in most of Little's books published since 1997, though usually only in passing as a place where characters have shopped, not as the evil entity it is portrayed as in the eponymous novel. The character Samantha from The Store is mentioned in The Resort, an amusement park called Familyland is mentioned in several books, and the Chinese restaurant where one of the main characters works in The Summoning is mentioned briefly in The Walking. These connections give the reader a sense of continuity between the works, as though all or most of Little's books take place in the same fictional universe.
There have been few adaptations of Bentley Little's work. However, Little's short story "The Washingtonians" was adapted by the horror anthology Masters of Horror under the direction of Peter Medak.
In 2007, the Hollywood Reporter reported that a film adaptation of The Store, which concerns a small Arizona town being slowly consumed by an evil corporate retail chain, is under works by Strike Entertainment. The script is to be adapted by Jenna McGrath, with production duties handled by Marc Abraham and Eric Newman, and executive production by Vince Gerardis, Eli Kirschner and Tom Bliss.