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".
Lean, mean Texas Ranger Jack Benteen locks horns with a former friend, Cash Bailey, now a ruthless drug kingpin. Though they're on opposite sides of the law, they share a love interest in the sensual Sarita. When a crew of rogue soldiers descends upon the border town for an off-the-books mission, all roads lead to a bloody, to-the-death showdown, as loyalties shift and the lines between good and evil are blurred.
A stage headed West with a group of passengers is attacked by Cheyenne Indians, and takes refuge in a nearby ghost town.
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.
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.
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.
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.
Jim Bannon and his partner own a stagecoach line. With the coming of the telegraph and the end of the Pony Express, two men plot to take over and get the new mail contract. When Jim's partner is murdered and Jim's name is written in the sand beside the body, Jim is arrested. At his trial Whip brings surprising evidence that clears Jim and the two plotters are soon arrested.
Countess Franziska "is kidnapped" by a band of robbers. However, her father is not willing to pay the ransom so Franziska changes sides.
Chasing jewel thieves, Captain Carson and Magpie head for the border where Carson, posing as a Chinaman, opens a store that buys jewelry. To flush the thieves into the open, Carson wins all their money at poker. They agree to sell him the jewels but plan to kill him and keep both the jewels and the money.
Bounty hunters seek shelter from a raging blizzard and get caught up in a plot of betrayal and deception.
A group of people traveling on a stagecoach find their journey complicated by the threat of Geronimo, and learn something about each other in the process.
In the late 19th Century, Mary Breydon, a widow, and Peggy Breydon, her daughter manage a stagecoach stop on The Cherokee Trail. The story is told from the perspective of Peggy, looking back on her adventures.
The Trail Blazers are bringing in a prisoner to stand trial for bank robbery, when several attempts are made to kill him; convinced of the man's innocence, they arrange a trap for the real thieves.
Lin McAdam rides into town on the trail of Dutch Henry Brown, only to find himself in a shooting competition against him. McAdam wins the prize, a one-in-a-thousand Winchester rifle, but Dutch steals it and leaves town. McAdam follows, intent on settling his old quarrel, while the rifle keeps changing hands and touching a number of lives.
Questions arise when Senator Stoddard attends the funeral of a local man named Tom Doniphon 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. 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.
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.
After Cacopoulos manages to save himself from being hung on a false charge, he robs Cat Stevens and Hutch Bessy of a lot of money and steals their horses. This results in a merry chase and Stevens and Bessy become unwilling allies in Cacopoulus' revenge against the people who deserted him and framed him to get their money back.