Joe Bonham, a young soldier serving in World War I, awakes in a hospital bed after being hit by a mortar shell. He gradually realizes that he has lost all of his mobility and his senses except for touch - he has lost his arms, legs, eyes, nose, ears, tongue, both jaws and all of his face - but that his mind functions perfectly, leaving him a prisoner in his own body. He tries to die by suffocating himself but he has been given a tracheostomy, which he cannot remove or control. He attempts to communicate with his doctors by banging his head on his pillow in Morse code. His wish is that he may be put in a glass tube and tour the country, to show people the true horrors of war. His wish to die is never granted, however, and it is implied that he will live the rest of his natural life in this condition.

As he drifts between reality and fantasy, he remembers his old life with his family and girlfriend, and reflects upon the myths and realities of war. He also forms a bond, of sorts, with a young nurse who senses his plight.

The title comes from the phrase "Johnny get your gun", a rallying call that was commonly used to encourage young American men to enlist in the military in the late 19th and early 20th century. That phrase was popularized in the George M. Cohan song "Over There", which was widely recorded in the first year of American involvement in World War I; the versions by Al Jolson, Enrico Caruso and Nora Bayes are believed to have sold the most copies on phonograph records at the time.

On March 9, 1940, a radio adaptation of Johnny Got His Gun was produced and directed by Arch Oboler, based on his script, and presented on the NBC Radio series "Arch Oboler's Plays." James Cagney played Joe Bonham on that broadcast.

Johnny Got His Gun was adapted into a stage play by Bradley Rand Smith in 1982, and has since been performed all over the world. Its first, off-Broadway run starred Jeff Daniels.

In 1971, Trumbo directed a film adaptation of the novel, starring Timothy Bottoms as Joe Bonham. The novel was adapted to film again in 2008, starring Benjamin McKenzie in a "Live on Stage, On Film" production.

Clips of the 1971 film version were used in the music video for the Metallica song "One". The song itself comes from an idea presented by drummer Lars Ulrich to singer James Hetfield that was very similar to the book. Instead of enduring a long and arduous negotiation for rights to the film, Metallica decided to buy the movie outright, in order to use it in their video. Also, "Johnny Got his Gun" is the main phrase of the chorus in Rular Rah's song "Johnny", which was also the theme music of "Derailed".

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