The central and overt themes in The Exorcist are metaphysical in essence: What constitutes humanity? How can one reconcile the existence of evil with the belief in a kind and benevolent God? The epigraphs of the novel's three parts demonstrate a journey from confronting the problem of evil—both supernatural and human—to St. Paul's affirmation of faith and love. These themes are woven into the storyline and are also explicitly debated by the characters, especially Father Karras and Lieutenant Kinderman, which some critics considered to be excessively expository.

Interwoven with specific societal issues, The Exorcist delves into the deep-seated fear of death and the potential for nothingness afterward. On the night when Regan first shows signs of possession, marked by the knocking sounds her mother hears, Chris MacNeil has a vivid dream about "death in the staggering particular," repeatedly thinking, I am not going to be, I will die, I won't be, and forever and ever . . . . In his work, I'll Tell Them I Remember You (1973), Blatty reflects on his mother's passing and describes his own "half-waking dream of death that had left me convinced it meant final extinction," which evidently inspired Chris's dream. The novel presents possession as a positive element, affirming the existence of non-physical realms. In Legion (1983; see separate entry), this concept broadens to encompass the confirmed survival of the human soul beyond death.

Ironically, while possession can mitigate the dread of dying, it introduces a new fear: the destruction of one's identity. As Noel Carroll points out in The Philosophy of Horror (1990), possession poses a threat to one's personal identity. Many readers or viewers may relate to Chris as a helpless parent, but there is also a disturbing link to Regan. Her involuntary changes, such as the phrase "help me" appearing on her skin as her only way to communicate, stir fears of madness, illness (her frail and infected-looking body), and other afflictions that torment both the body and mind.

Additionally, there are similarities between Regan's domination by the demon and the Engstroms' daughter’s struggle with heroin addiction.

Parent-child dynamics play a crucial role in the novel, impacting both personal and societal aspects. Although the overall outlook is rather grim, each relationship manages to reach some form of resolution. An example of good arising from bad, often missed by critics, is Kinderman's connection with Engstrom's daughter. His investigation into Karl Engstrom as a suspect in Burke Dennings' murder ultimately results in her entering a rehabilitation clinic—an outcome her father's love alone could not achieve. While Regan's return to her original state may seem adequate, there are also signs of a deepened connection between mother and daughter. In the epilogue, as they head back to their home in Los Angeles, Chris and Regan walk together, hand in hand. Although there is no hint of the marriage rekindling, Chris begins to correct those who address her as Miss MacNeil, reclaiming her identity as "Mrs." even if it doesn't include her former husband.

The most captivating relationship in The Exorcist is the bond between Father Karras and his mother. Blatty has revealed that Karras's mother is closely modeled after his own. Interestingly, events from both the novel and film versions of The Exorcist also appear in Blatty's memoir about his mother. In I'll Tell Them I Remember You, he describes a dream he had after his mother's passing, where she surfaces from a subway kiosk, yet his dream-self cannot reach her. This scene is movingly portrayed in the film. Blatty also recounts a story about his mother trying to comfort him with money after his dog succumbed to distemper; this tale, including the dog's name, is echoed when Regan, possessed, speaks with Karras's mother's voice. It can be deduced that Blatty began to process his emotions regarding his mother's death in the novel, which enabled him to address these painful issues more openly in his memoir.