Brian Lumley added to H. P. Lovecraft's Cthulhu Mythos cycle of stories, including several tales featuring the character Titus Crow. Others pastiched Lovecrafts's Dream Cycle and featured the characters David Hero and Eldin the Wanderer. Lumley once explained the difference between his Cthulhu Mythos characters and Lovecraft's: "My guys fight back. Also, they like to have a laugh along the way."

Later works included the Necroscope series of novels, which produced spin-off series such as the Vampire World Trilogy, The Lost Years parts 1 and 2, and the E-Branch trilogy. The central protagonist of the earlier Necroscope novels appears in the anthology Harry Keogh and Other Weird Heroes. The Necroscope saga is closed with the novel The Touch.

Lumley served as president of the Horror Writers Association from 1996 to 1997. On 28 March 2010 got Lumley the Lifetime Achievement Award of the Horror Writers Association. He also received a World Fantasy Award for Lifetime Achievement in 2010.