The novel's themes mirror its complex duality. Although aggression is a central concern—much like in the film—Moon-Watcher learns not precision in targeting, but the art of killing. On multiple occasions, the act of sighting is entwined with the use of a telescope or a radio antenna; the monolith on the Moon stands firmly at the center, both in Tycho and at the heart of its magnetic pull. The narrative thereby intimates that aggression and communication are two sides of the same coin, each finding its true purpose only when combined. It is from this amalgamation that society springs forth.

A central motif, much like in Childhood's End and The City and the Stars (1956), is the elevation beyond the tangible realm. The mind yearns to attain the serenity of an inorganic crystal, reminiscent of the extraterrestrial beings who have transcended a mechanized existence "to enshrine their thoughts for eternity in frozen lattices of light." This crystalline symbolism permeates the narrative, manifested in the looming monoliths, the silent hibernacula, the haunting strains of Bach's music that Bowman absorbs after the demise of his comrades, and in the Eye of Japetus, which draws him in for transformation.

While the novel champions the power of collective effort, its characters grapple with a profound solitude, breaking free only by merging into a glacial collective consciousness.

An underlying motif woven through these narratives of unraveling the unfathomable and sidestepping the connection between hostility and dialogue is the portrayal of guilt. Engaging in conversation with Hal following its lethal act against Poole, Bowman experiences the sensation of being interrogated "for a crime of which he was unaware." This guilt unmistakably stems from his human accountability for the clandestine actions that triggered Hal's deadly descent into madness. Clarke's benevolent humanity finds itself ensnared in a predicament: the bonds that tie communication to hostility and subsequently to guilt, while secrecy spirals into alienation and defensive ruptures. The unavoidable journey through reality is fraught with panic and guilt.