Bounty hunters seek shelter from a raging blizzard and get caught up in a plot of betrayal and deception.
In order to obtain a stage coach mail contract, a new road must be built. A gang of outlaws try to prevent the building of the road.
Jesse W. Haywood (Don Knotts) graduates from dental school in Philadelphia in 1870 and goes west to become a frontier dentist. Penelope "Bad Penny" Cushing (Barbara Rhoades) is offered a pardon if she will track down a ring of gun smugglers. She tricks Haywood into a sham marriage as a disguise. Haywood inadvertently becomes the legendary "Doc the Haywood" after he guns down "Arnold the Kid".
After her stagecoach is ambushed, a woman is tasked with holding a dangerous outlaw captive and must survive the day when the bandit’s gang tries 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.
The two brothers Trinity and Bambino are exchanged by two federal agents and take advantage of the situation to steal a huge booty hidden in a monastery by a gang of outlaws.
Bandit Cheyenne Harry reforms because of the faith placed in him by Molly Young and her father. Soon, however, Harry is lured from the straight and narrow when he meets his old friend Ben Kent and consents to participate in Kent's plan of robbing a stagecoach.
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 cowboy turns bounty hunter to pay off his debts.
Questions arise when Senator Stoddard (James Stewart) attends the funeral of a local man named Tom Doniphon (John Wayne) in a small Western town. Flashing back, we learn Doniphon saved Stoddard, then a lawyer, when he was roughed up by a crew of outlaws terrorizing the town, led by Liberty Valance (Lee Marvin). As the territory's safety hung in the balance, Doniphon and Stoddard, two of the only people standing up to him, proved to be very important, but different, foes to Valance.
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.
The coming of the railroad to Cedar City spells the end of the stagecoach as the government gives the mail contract to the fastest means of delivery. McCord loses the stagecoach line gambling with the new buyer, but has enough hidden money to buy a ranch and some cattle. To make more money, he starts a gang to rob the railroad, express offices and steal cattle. But the railroads send out special agent Cameron to end his reign of violence.
After the train station clerk is assaulted and left bound and gagged, then the departing train and its passengers robbed, a posse goes in hot pursuit of the fleeing bandits.
Outlaw Jesse James is rumored to be the 'fastest gun in the West'. An eager recruit into James' notorious gang, Robert Ford eventually grows jealous of the famed outlaw and, when Robert and his brother sense an opportunity to kill James, their murderous action elevates their target to near mythical status.
A young woman arrives in the western town of Headstone and helps the locals outsmart a gang of outlaws.
The conflict between a railroader and a stage line owner is being aggravated by bad guys who are sabotaging both sides. Roy and Gabby mediate the conflict and expose the bad guys.
Crooked ranch foreman Thatcher sends his two henchmen, Parnell and Clint, out to murder his boss, wealthy Peter Arnold who has just arrived to retire on his ranch, bringing in tow his daughter, tomboy Jessie, who despises western life and can't wait to run off back to San Francisco. Stagecoach line owner Dave Collins and his sidekick Chito show up just in time to deter the attackers. Collins isn't done yet, though, as a gold shipment sent on one of his stages is stolen by Parnell and Clint, one of whom is recognized by Jessie, attempting to escape back to the west coast. Collins has his hands full trying to retrieve the stolen gold, and dealing with Jessie, who's fallen head-over-heels in love with him.
Lash and Fuzzy sent to help John Watson with his stage line arrive to find him murdered. Recognizing the outlaws they trail them to their leader Baxter. But before Baxter can tell who the big boss is he is shot. After getting the stage through to assure the mail contract, Lash now realizes who the boss is.
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.
Double-crossed and left without water in the desert, Cable Hogue is saved when he finds a spring. It is in just the right spot for a much needed rest stop on the local stagecoach line, and Hogue uses this to his advantage. He builds a house and makes money off the stagecoach passengers. Hildy, a prostitute from the nearest town, moves in with him. Hogue has everything going his way until the advent of the automobile ends the era of the stagecoach.