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.
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.
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.
A stage headed West with a group of passengers is attacked by Cheyenne Indians, and takes refuge in a nearby ghost town.
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.
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.
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 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.
As prisoner Ed Archer is being transferred, the stage is attacked and crashes. Archer escapes the attackers but Ranger Rocky Lane catches up with him. As Rocky is bringing him in, Archer is attacked again. Somebody wants Archer killed and Rocky, now suspecting Archer is innocent, decides to find out who and why.
A bandit disguises himself as an officer in an attempt to woo a saloon singer.
At a desolate relay station in the west, a stagecoach attendant and a stranded woman traveller are held captive by a band of escaped convicts.
An independent former ranch foreman and an heiress are kidnapped by a trio of ruthless outlaws.
After a stagecoach holdup, Frank Slayton's notorious gang leave Ben Warren for dead and head off with his fiancée. Warren follows, and although none of the townspeople he comes across are prepared to help, he recruits two others who have sworn revenge on the ruthless Slayton.
A small-town sheriff in the American West enlists the help of a disabled man, a drunk, and a young gunfighter in his efforts to hold in jail the brother of the local bad guy.
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.
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.
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.
Bounty hunters seek shelter from a raging blizzard and get caught up in a plot of betrayal and deception.
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.
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".