Derleth wrote a great deal of fiction in the Cthulhu Mythos, and his first collection of stories in this realm was the Mask of Cthulhu (1958). The Trail of Cthulhu (1962) is a collection of short fiction featuring Dr.

Laban Shrewsbury. Previously uncollected Cthulhu Mythos short fiction and all the stories from the Mask of Cthulhu and The Trail of Cthulhu were included in The Cthulhu Mythos (1997). The Survivor and Others (1957) and The Watcher Out of Time and Others (1974) include Derleth's completions of stories begun but not finished by Lovecraft and stories based on fragments by Lovecraft.

The Lurker at the Threshold (1945) is a novel derived from two Lovecraft fragments.

Derleth sought to give form and consistency to the frightful universe created by Lovecraft, and in this he differed markedly from the older author. Lovecraft sought to reveal a cosmos of uncaring chaos so indifferent to man that...