When his herd is wiped out by Texas Fever, Cheyenne is asked by a beautiful woman to help push her herd which carries the fever through a quarantine. He soon realizes she has other plans for him nor does want to infect more cattle.
Cheyenne rides into town and is quickly arrested on a trumped up charge. He finds that the same is happening to every unemployed person or drifter who comes into the town, and they are being forced to work on a chain gang in a mine.
Cheyenne is hired by the Army to bring in Capt. Robert Holman who deserted after being accused of murdering an Army hero who was massacred by the Comanches. Unconvinced Holman is guilty, he takes it on himself to prove his innocence.
Cheyenne visits an old friend only to find him in a wheelchair. His son is a loner, laughed at by the town. He wins a rifle in a contest but runs away when the town wants to lynch him for an act of self defense.
After being fired in one town, Cheyenne is hired to help another town rid itself of a clan who have held them in their grip for too long. With the help of a wanted outlaw who once saved his life, he reluctantly accepts the job.
The citizens of Lehigh rejoice when the bank is robbed when Sheriff Bodie is out of town. It seems that the banker is the most hated man in town, nobody was sorry to see his bank robbed, and they definitely do not want the robbers caught.
Cheyenne rides into a town as the bank is being robbed. He stops the robbery and the money is recovered but the two bandits who escape kidnap the orphaned son of a convict and owner of the saloon as the son asks Cheyenne for help.
Cheyenne finds out he may be John Abbot, the long lost son of one of the wealthiest men in the country. Doubts creep in the more he finds about his family and his father's deep-seated hatred for White Cloud, his Indian father.
Cheyenne rides to Salt Lick to buy a Brahma Bull to aid the recovery of a sick child. When he runs into some outlaws on the trail he's saved by a stranger who has trouble explaining why his name doesn't match the initials on his gun.
Small-time bandit rises to claim he is dictator of a Mexican province. He demands a tax payment of the wedding rings of the villagers. Harold J. Stone plays Perez.
Cheyenne hires out to take some passengers to Creek Point unaware he is heading into danger. One is a crippled gunfighter who was tormented while in prison and still has nightmares about killing a small boy by accident.
Cheyenne takes a train ride to Denver. His mission? Transporting Cole Younger to prison. Little does he know there are plans to break him out and the first to draw on him is a small boy with a toy pistol and son of a beautiful widow.
When four men receive letters predicting their deaths, Cheyenne is the only one who recognizes the danger they bring. Pretty Penelope Piper arrives on the stage and the deaths start - each with her involved but the men trust her.