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.
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.
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.
A band of outlaws, led by "Papa" Clellan, hold up in a ghost town as they plan an attack on a wagon train loaded with gold. The unexpected arrival of a stagecoach forces the gang to hold the passengers and driver as hostages. The later arrival of a wanderer, John Trey, sets in motion events not in "Papa" Clellan's original plan.
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.
During the California Gold Rush, two down-on-their-luck vaudevillians attempt to become wealthy by bringing a girlie show to an all-male western mining town.
Traveling north into Arizona, Cisco finds that someone committing robberies has been impersonating him and he is a wanted man. After retrieving some of the stolen loot, he is caught with it in his posession and put in the guard house. A friend whose life he recently saved beaks him out and Cisco heads out to find the impersonator and clear himself.
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.
In Old California, a young Frenchman transporting a chest full of silver travels by stagecoach to San Marino, to complete a complex business deal. The stagecoach is ambushed by a band of men whose leader, a mysterious bandido known as Cisco (Gilbert Roland), claims the silver is money that was extorted over a period of years from the poor people of California. The bandits take the money and escape, but Cisco stays behind with the Frenchman -- who, it turns out, is actually a lovely mademoiselle, Jeanne DuBois (Ramsay Ames). She follows him to the bandit's lair, where Cisco tells her he intends to return the stolen money to the poor people. The two rivals are irresistibly drawn to each other, however, and as a token of love Cisco offers to return the money to Jeanne instead. Now she must decide whether to complete her business deal, or to comply with Cisco's wishes and redistribute the wealth.
The Cisco Kid (Gilbert Roland) sets out on a double mission of rescuing a girl from forsaking her true love by marrying a supposedly wealthy suitor to save the old family hacienda, and he is also after the outlaws that robbed a stage carrying gold for the Mission. His task is made easier once he learns that the "wealthy" suitor (Tristram Coffin) is also the man behind the gold robbers.
The Cisco Kid (Gilbert Roland) hears of a land-swindling scheme devised by the police Commandante (Martin Garralaga) and the tax collector (Harry Woods) in a small western town. Cisco's efforts against the plot cause the thieves to fall out, and Cisco is able to return the land to the rightful owners.
Chasing women and staying one step ahead of the law, the Cisco Kid meets Raquel and then Dolores. He sees that Raole is the boy friend of Raquel but engaged to Dolores. Learning that all her money will got to her uncle Don Jose when she marries Raole, Cisco suspects a plot and sets out to unravel it.
Eduardo Belmonte overhears his new step-mother, Maria, and her lover, Don Ricardo Gonzales plotting to take over the Belmonte rancho on the night of the fiesta given by her husband, Don Carlos Belmonte. Eduardo offers Maria money if she will depart the hacienda premises, but she refuses and then accuses Eduardo of making love to her. The old Don doesn't take kindly to his son hitting on his step-mother and attacks him in a rage. The lights go out, the father is killed and Maria blames Eduardo, who escapes from the house, chased by Ricardo's men. The Cisco Kid and Pancho rescue Eduardo, who has been shot, and hide him while they investigate. Cisco discovers that bullets from Maria's gun, a handy little derringer, are the same type that killed Don Carlos. But the Alcalde arrests Cisco and Pancho, and Cisco is "supposedly" executed by a firing squad, but IS NOT shot and escapes by a trick. And now Maria and Ricardo are in real trouble with Cisco on the loose.
A young woman arrives in the western town of Headstone and helps the locals outsmart a gang of outlaws.
Stage line owner Brent has his men robbing Halliday stages and when his manager Waring learns of it, Brent has him killed. Jeff Waring arrives and takes his uncle's job. He soon learns what's happening and the Durango Kid goes into action. This keeps Halliday going and gives them a chance to get the mail contract by winning the stagecoach race.
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.
When Rocklin arrives in a western town he finds that the rancher who hired him as a foreman has been murdered. He is out to solve the murder and thwart the scheming to take the ranch from its rightful owner.
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.
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.
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".