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.
A peace-loving man named Ben Kane takes a job as deputy marshal of Lords, in the old West. Kane is no lawman, but he accepts the badge because he has an old score to settle with the town’s chief trouble-maker. Once on the job, Kane must also deal with a young sharpshooter named Billy Young and a sharp and sassy saloon dancer, Lily.
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”.
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.
A group of unlikely travelling companions find themselves on the same stagecoach to Cheyenne. They include a drunken doctor, a bar girl who’s been thrown out of town, a professional gambler, a travelling liquor salesman, a banker who has decided to embezzle money, a gun-slinger out for revenge and a young woman going to join her army captain husband. All have secrets but when they are set upon by an Indian war party and then a family of outlaws, they find they must all work together if they are to stay alive.
Case Britton, gunslinger and wanted man, comes to town to meet his bride-to-be, stop a stagecoach robbery, and get even with the man who killed his brother.
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.