It is the story of Harrison Destry's quest for revenge against the 12 jurors whose personal malice leads them to wrongfully convict him of robbery.

Harrison Destry, a man who thinks he is better than anyone else and is constantly "proving" it by his skill with a gun, and his ability to win fistfights he provokes, has just lost his horse and his saddle in a card game.

Knowing Destry's character, Bent expects he will waste the money on liquor and gambling, rather than replacing his horse and saddle.

Destry explains he is determined to stay within the law from now on (though some of his actions, such as trespassing and safe-cracking, are of dubious legality).

Though running a fever, Willie steals a horse and makes a long, hard ride back to Wham to warn Destry of Bent's treachery.

Returning to the devoted Charlotte Dangerfield, Destry announces he will lay down his guns forever, acknowledging that he found his peer in Bent.

The time setting of Destry Rides Again is never explicitly stated, and obvious markers such as presidents or governors are not mentioned.

Denali Mountain in Alaska was not referred to as Mount McKinley until 1897, implying the events of the novel, particularly Destry's release, would have taken place around or after 1897.

In any event, the absence of references to motor cars or to any man having served in World War I suggests a setting no later than 1916.

Destry Rides Again was first published in 1930, in a series of installments under the title "Twelve Peers" in Frank Blackwell's Western Story Magazine.

These owe little to the novel other than their name; the plots are completely unrelated to Brand's story, and Destry's first name is also changed to Tom in the movies.