It was preceded by a tie-in comic book line published by Gold Key and the novel Mission to Horatius by Mack Reynolds, all intended for younger readers.

[1][2]: xi Blish aimed to kill off a popular character as a way to surprise readers, and during the novel's production chose Spock, with the aid of his wife, J.A.

Prior to the release of Spock Must Die!, Blish had written three collections of short stories adapting episodes of the television series.

The second collection, Star Trek 2 (February 1968),[5] included an adaptation of the episode "Errand of Mercy", which the novel directly references in the second chapter.

Scotty explains that the technology does not destroy the original object but causes every single particle to undergo a "Dirac jump" to its new location, and that converting a human-sized mass to energy would blow up the ship.

After faking a mental breakdown and barricading himself in sick bay, Spock One escapes in a stolen shuttlecraft which he has adapted to warp drive.

The crew find corroboration of this when they discover that Spock One used the Enterprise's science facilities to manufacture chirality-reversed amino acids.

McCoy explains that such a meager diet would have induced deficiency diseases in a human, but that a Vulcan is able to endure it indefinitely.

For the first original Star Trek novel for adults, Blish wanted to surprise readers by killing a popular character.

[2]: 10 The plot, featuring both the Klingons and the Organians, is a follow-up to the first season episode "Errand of Mercy", which had previously been adapted into a short story by Blish, published in Star Trek 2 (February 1968).

[7][6]: 37  Another alien species mentioned is the "reepicheep", based on the name of a Talking Mouse in Prince Caspian and Voyage of the Dawn Treader.

Instead, the Organians have confined the Klingon race to their homeworld for a thousand years, unable to take advantage of space flight, and the antagonist Commander Koloth is trapped in an asymptotically slowing distortion of local time, unaware of his punishment.

[4] In A Clash of Symbols (October 1979), Brian M. Stableford described the novel as a "combination of space opera and whimsy, quite typical of the Star Trek mythos".

[8] Strother B. Purdy referred to novel's text as a "rather well-written" example of the duplication of characters in science fiction, in his study The Hole in the Fabric (March 1977).

Purdy was also impressed by novel's play on elements in the vein of Martin Gardner's The Ambidextrous Universe and Lewis Carroll's Through the Looking-Glass.