Fate
To what extent Francis Wayland Thurston is ultimately fated to be the lone surviving interpreter of the Cthulhu mythos is an open question in the tale. Regardless, fate itself is a major theme in the story, as Thurston's attempts to uncover the truth behind the Cthulhu rumors are also aided by strokes of pure luck and good fortune, as when he initially notices Angell's secret manuscripts, or when he spots an issue of the Sydney Bulletin on a chance visit to a local museum. Lovecraft also weaves the theme of fate into the musings of the cultist elder Old Castro, who surmises dreamily that the "Old Ones" will rise when the stars achievement a certain alignment with human affairs. At the end of the story, Thurston himself wonders whether fate has in store for him the same kind of demise that claimed Johansen's and his grand-uncle's lives.
Writing
As an epistolary tale, "The Call of Cthulhu" consists of written documents left behind by Francis Wayland Thurston. Thurston's written document is itself an archive of other writings—his late grand-uncle's papers, various transcribed oral accounts, news clippings, a diary, and so forth. The transmission of the secrets of the Cthulhu cult through writing is a cursed act that dooms many of the tale's characters, including Johansen, Angell, and Thurston himself. The preponderance of written manuscripts in the story correlates inversely with the vague and suggestive fragments that each of the tale's speakers is able to convey, which limits Thurston's ability to understand their implications until he pieces them all together. Lovecraft represents writing as a lethal weapon, as when a cache of papers falls on Johansen's head, killing him, or when the acquisition of Johansen's diary ensures Thurston's assassination. The struggle to understand the alien hieroglyphics in the story is an impossible task that repeatedly claims the translator's life.
Dreams
Lovecraft first expresses the outline of Cthulhu in the form of a clay bas-relief glimpsed in the dreaming mind of an artist named Henry Anthony Wilcox. Dreams are the provenance of the very first pieces of evidence that Thurston receives from Angell's manuscripts about the Cthulhu cult, specifically the dreams of "hyper-sensitive" poets and artists like Henry A. Wilcox. Eventually, Thurston pieces together the fact that an unnatural earthquake on the night of February 28th triggered Wilcox's visions, and that Cthulhu's awakening on March 22nd intensified these visions into a delirium. Because mankind cannot directly know or comprehend the "Old Ones" without being driven insane, dreaming is the only way many of the story's characters are able to access their language and imagery.
Mystery
Lovecraft's tale often relies on the power of the unknown—specifically, how insignificant mankind seems in light of the incomprehensible nature of the universe. The opening lines of the story, probably the most famous lines Lovecraft ever wrote, articulate the nihilistic philosophy of a man who has come to know just how insubstantial human affairs really are, in the grand scheme of the cosmos. Many of the story's narrators are professors and detectives, vocations that entail combing through mysteries and gaps in knowledge to produce satisfying solutions and intellectual accounts. Wilcox's bas-relief, Legrasse's statuette, and Johansen's idol are all symbols of mysteriousness—objects that defy expert analysis, yielding no influences or translations. Mystery has a double function, in that it limits the characters' understanding of the cult, at the same time that it intrigues them into further study.
Horror
"The Call of Cthulhu" aspires to represent a horror that is beyond describability—monstrous cosmological forces that defy rational human modes of communication like writing and speech. The story's first part, entitled "The Horror in Clay," suggests that the only way humans can glimpse the ancient depths of horror that Cthulhu represents are in dreams and nightmares. Thurston refers to his revelations toward the end of the story as "cosmic horrors" which eventually disturb his sleep, derange his mind, and make him a target for assassination. At the end of the story Thurston remarks, "I have looked upon all that the universe has to hold of horror." Lovecraft demonstrates how the human constitution is not built to endure knowledge about the horrors of the universe, hence why the opening lines of the story praise the "inability" of the human mind as merciful.
Obsession
The driving mysteries at the heart of the Cthulhu cult, in spite of their horrifying nature, compel the men in the story to learn more about them, and even to dedicate their lives to deciphering their secrets. Hearing Wilcox's dreams, for instance, drives Angell to record the dreams of other artists and laypeople, in hopes of divining patterns in their dreamwork. Thurston is so intrigued by Angell's manuscripts that he travels to Louisiana to interview Legrasse, and the surviving prisoners apprehended in a police raid on a Cthulhu cult ritual. Upon becoming captain of his unit, Johansen insists on piloting his ship toward what turns out to be Cthulhu's resting place. The suggestively horrifying glimpses of the cult's secrets lure many of the men in the tale toward the blinding truth—and ultimately, madness and death.
Mythology
Lovecraft's tale takes place in an extended universe that has come to be known as the "Cthulhu Mythos." The cosmological forces in Lovecraft's fiction extend far beyond the outer reaches of the universe, as well as the boundaries of recorded time. Lovecraft uses mythological allusions, in particular to the Cyclops, to describe the primordial race of gigantic creatures known as "Great Old Ones." Old Castro is the character in the story who seems to have the most extensive knowledge about the ancient history of these entities and their role and function in the universe. Lovecraft embeds fantastic and horrific descriptions of mythical creatures in the highly notational and archival style typical of the epistolary genre, so that they seem like uncovered realities, rather than absurd confabulations.