A stage headed West with a group of passengers is attacked by Cheyenne Indians, and takes refuge in a nearby ghost town.
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Dan Evans, a small time farmer, is hired to escort Ben Wade, a dangerous outlaw, to Yuma. As Evans and Wade wait for the 3:10 train to Yuma, Wade's gang is racing to free him.
Union officer Kerry Bradford escapes from a Confederate prison and races to intercept $5 million in gold destined for Confederate coffers. A Confederate sympathizer and a Mexican bandit, each with their own stake in the loot, stand in his way.
John Russell, disdained by his "respectable" fellow stagecoach passengers because he was raised by Indians, becomes their only hope for survival when they are set upon by outlaws.
Stodge City is in the grip of the Rumpo Kid and his gang. Mistaken identity again takes a hand as a 'sanitary engineer' named Marshal P. Knutt is mistaken for a law marshal. Being the conscientious sort, Marshal tries to help the town get rid of Rumpo, and a showdown is inevitable. Marshal has two aids—revenge-seeking Annie Oakley and his sanitary expertise.
A gang of bandits takes control of Tucson in preparation for the arrival of a consignment of gold, with only a band of voluntary soldiers trying to outwit them and save the town.
The arrival of the telegraph put Pony Express riders like John Blair and his pal Smoky out of work. A race will decide whether they or stageline owner Drake get the government mail contract.