Little Joe puts his life on the line to help sick friend-turned-gunfighter, Steve Friday, who is holed up in a second story hotel room and waiting a challenge from a gunman, hired by the father of one of Friday's victims to avenge his son's death on the anniversary of the killing... Friday the 13th.
Ben visits his old friend Paul Rowen, the sheriff of Concho. His wife Katherine says he has been complaining of headaches for six months now. When he starts shooting innocent people he swore to protect, the whole town has to decide how best to keep from killing their good friend.
Initially suspected as being part of the bank-robbing Hollister gang while on his way to visit Tom and Ellie Blackwell's drought-stricken ranch, Little Joe is soon held hostage and his friends terrorized by the real desperadoes on the run to Mexico with a wounded man.
While riding posse after a band of vicious marauders led by a renegade ex-cavalry officer, Ben Cartwright captures a wounded comanchero and tries to protect him from the angry ranchers who want to lynch him, his own gang who wants the money he was carrying for them and an angry Little Joe who lost a friend when his ranch was raided.
A marshal's brother is shot by two men who held up the stage depot. Little Joe joins the posse who follows the trail left by those men. They come upon two men who say they didn't do it but since his brother may die, the marshal seems to have other ideas.
Matt Jeffers is about to lose his land. Back taxes, no water and owes his foreman wages. When his foreman finds water on the land he hatches a scheme to buy the land and stick Little Joe with all the blame.
A pretty woman arrives by stage and places this Notice up: I will pay $1000 to the man who kills Joe Cartwright in a fair fight. When he finds out the story behind it, Joe tries to convince her she is wrong. Failing that, someone has already picked up the gauntlet to see Joe Cartwright dead.
Joe and Hoss are out when they are attacked by Indians, Joe hit with an arrow. With Joe needing medical attention, they come across a small wagon train of misfits, heading East. Their only doctor, dying and wanting to see his grandchildren before he dies, helps Little Joe.
Ben militia troop is reactivated when the Paiute Indian Wabuska is captured and needs to be transported to the nearest fort. The Indians consider him to be a god which makes him very important to their people. When several of the soldiers are killed, the tribal chief sees for himself what they have been dying for.
Donnie Buckler has been shot getting away from a holdup. He buries a portion and then is found by Little Joe. They go to the Ponderosa and fetch the doc but by the time he arrives the Cartwrights have been seized by the rest of the gang. When Donnie doesn't give up the loot's location, the boss decides to use some different leverage - an old girlfriend he hadn't seen in about a year.
Joe, Hoss and Candy drive a herd to Sand Dust. When they go into town to collect their wages, the buyer is robbed and killed with four witnesses to both crimes. When they are put up in the hotel under protective custody, the Slater gang makes several attempts to finish them all off so they can't testify against the one brother they managed to capture.
When their parents died, Mark's older brother raised him at times like he was breaking a horse. Part because he was just a kid himself and others because he didn't know any better. But Mark never doubted his brother's love but he has to show a new girl in town or die trying.
Ben Cartwright (Lorne Greene) buys a teen-age girl's stallion from her father, Burt Loughlin (Tom Tully), with the intention of letting the girl, Trudy Loughlin (Kim Darby),ride the horse in a high-stakes race, but his plans are upset when the father falls in with Harper (William Bryant), a crooked gambler.
The Cartwrights become unwitting pawns in a battle between wealthy rancher Gabriel Bingham and his penniless nephew Jayce Fredericks over the ownership of the valuable black horse Jayce needs to restart his herd and reclaim his ranch.
Not long after bad-tempered Frank Scott is hanged for murdering a young woman in a dark Virginia City alley, witness for the prosecution, Hoss Cartwright, sees a man in a Carson City saloon who looks just like Frank, hears him whistling the same strange tune the killer whistled that fateful night, and begins to fear that his testimony has sent the wrong man to the gallows.
Wally Cox is the inventor of a "Willy Wonka like" machine, which he sells to Hoss claiming it has the ability to detect gold. However, all it can really detect is the lie behind the 'gold detection' theory.