With the end of the American Civil War, military industrialists are left with an oversupply of weapons. Some of the more unscrupulous ones view the Indians as possible new customers. Wild Bill Hickok has just been discharged from the Union Army and is making his way back west. On a paddle steamer, he bumps into his old army scout colleague, Buffalo Bill Cody and his new bride. Later, Calamity Jane is the driver of their stagecoach to Hays City, Kansas. John Lattimer, an agent for the gun makers, has supplied the Cheyenne Indians with repeating rifles, which enable them to kill half of the troopers at a United States Cavalry outpost. Hickok discovers the rifles and reports it to General George Armstrong Custer. Custer sends out an ammunition train to the fort with Cody as guide. Hickok tries to locate Yellow Hand, the Cheyenne chieftain, to find out why the Indians have gone to war. When Calamity is captured by the Indians, Hickok tries to bargain for her release, but instead gets captured himself. Yellow Hand states that the Indians are fighting because the white man has starting settling land promised to the Indian and is killing off the buffalo. Yellow Hand promises to release his captives if they tell him the location of the ammunition train. After much prodding from Calamity, Hickok professes his love for her just before he is about to be tortured. Calamity then discloses the route of the ammunition train in order to save Hickok from being burned alive. Yellow Hand holds true to his word by releasing his two prisoners. The Indians ambush the ammunition train. Hickok sends Jane to get reinforcements while he fights alongside the besieged soldiers. After a desperate six-day siege on a river bank, the survivors are saved when Custer arrives with the cavalry. Back in town, Hickok catches up with Lattimer and tells him to get ready for a gun duel. Instead of going himself, Lattimer sends three cavalry deserters in his place. Hickok kills all three deserters in the gunfight, but this makes him a fugitive from the law. Hickok flees to the Dakota Territory. Calamity leaves for Deadwood separately when the townspeople find out that she was partly responsible for the attack on the ammunition train. Custer sends Cody after Hickok. After meeting in the woods, the two friends capture an Indian and learn that Custer has been killed at the Battle of the Little Bighorn and that the Cheyenne are moving to join the Sioux Indians in the Black Hills. They also learn that Lattimer is sending more rifles to the Indians, to be picked up in Deadwood. Instead of arresting his friend, Cody rides off to warn the cavalry, while Hickok goes to Deadwood to deal with Lattimer. Hickok kills Lattimer and detains Lattimer's henchmen for arrest by the cavalry. Hickok is shot in the back by Lattimer's informant Jack McCall while he is playing cards with the henchmen. The film ends with a heart-broken Calamity Jane cradling Hickok's body.
Writing for The Spectator in 1937, Graham Greene gave the film a rave review, suggesting that "perhaps it is the finest Western in the history of film". Greene praises de Mille's direction for his "magnificent handling of the extras in the big sets" as well "the firm handling of the individual drama". He also describes his pleasure in the acting of Cooper and Bickford as well as the "unexpected trace of sophistication" in Antheil's soundtrack for the film. Today the film is recognized by American Film Institute in these lists:
