Simon Kane drubs his supervisor Osgood for revealing that Kane's wife deserted him and his son. Kane had been working off the $2000 he embezzled to search for his wife, but Osgood's taunts made his life miserable, so now the single father can't face further derision from the town. Kane pays Osgood $2000 and packs to start over elsewhere. But Osgood hires an assassin to bump off Kane after his stagecoach heads West.
Though Luke & Simon foil a gunman who provokes a passenger on their first stagecoach run, the vicious gunslinger tracks the stage. He's a detective hired to break up a naïve young couple eloping from the East. To protect her groom, Sarah Lou claims it's her idea to return home. Luke, Simon, and Simon's son Davey are excited to be on the journey, because the destination is their new home, Outpost.
While on their regular stagecoach run Simon and Davey Kane pick up a man walking by the road in the middle of nowhere. Their new passenger takes an unusual interest in their only cargo - a coffin. The Kanes soon learn that the man is the leader of an outlaw gang who plans to hold the contents of the coffin, the remains of a dead war hero, for ransom.
A wounded Mexican tries to hijack Luke's stagecoach to steal a horse, but passes out from loss of blood before he can ride away. Luke bundles the man into his stage intending to turn him over to the sheriff in the next town, but a gang of bounty hunters try to abduct his prisoner in order to take across the border to stand trial for treason.
During a ferocious sandstorm, Simon Kane spots a man lying by the side of the road. When he stops his stagecoach and attempts to render assistance, he discovers that the "body" is alive and well - and the junior member of a pair of bank robbers who will stop at nothing to escape the pursuing posse.
Simon Kane takes an interest in a fight between two Civil War veterans when his son is injured by a runaway wagon whose horses bolted during one of their fights. Kane learns that Leo Calloway blames Toby Reese for fleeing the battlefield after he was badly wounded and Reese, tired of running from Calloway, is prepared to make a stand.
A young man is given a free stagecoach ride by Simon Kane to the stagecoach relay station. At the station, the man confesses that he is an escaped prisoner who, upon learning he has less than a year to live became determined to spend Christmas with his wife and children. He promises to turn himself in on December 26, but three bounty hunters are determined to collect the reward for his capture before then.
Simon Kane offers a British sailor a ride in his stagecoach when he spots him standing forlornly by the side of the road. The sailor tells Simon he jumped ship in San Francisco and a band of men have been chasing him ever since. The five men, all federal marshals, surround Simon's stagecoach and tell him that his newest passenger fled a ship that contained bubonic plague and they were authorized to kill everyone the Britisher came in contact with to prevent the diseases spread.
A couple engaged to be married buy all the tickets for the westbound run from Timberline, booting off Mr. Duncan, one of the scheduled passengers, in the process. When the stagecoach stops at the next way-station, Luke discovers that an outlaw gang was planning on robbing Duncan of the $20,000 he was carrying. Since their intended victim wasn't on-board, the owlhoots decide to hold the other passengers for ransom.
Simon and Davey find Deborah Cotton and her daughter standing on the bank of river and agree to give them a ride into Outpost. The two women are fleeing a private detective who has been hired to arrest Deborah for kidnapping her own daughter. When Simon appears reluctant to assist the Cottons, Davey decides to act on his own and obstruct the detective's pursuit.
A famous singer arrives in Outpost to deliver a concert and is welcomed by the entertainment starved community. When a stray bullet seriously wounds the chanteuse, the townspeople discover the goddess they idolized is really a foul-tempered and selfish shrew. After her business manager abandons her, only Vernon, a patient deaf-mute, is willing to tend to her many needs, but the singer scorns his pity.
Finn McCool joins the stage, not telling Kane that he is being pursued by members of the Irish Republican Brotherhood, who believe he betrayed them. A man with a lot of braggadocio and blarney and little respect for custom, Finn finds an admirer in young Davey, but Simon doesn't like it when Finn begins to make moves on the wife of an English fellow passenger.
Ethan Blount, a once famous attorney, now a drunken old man, is forced to prosecute a case for murder where the defendant is the son of the town's leading businessman. Blount is ordered to lose the case or else, but when the town boss pulls down a statue of Justice that the aging lawyer paid for, the old man refuses to back down in spite of death threats.
Simon Kane and Zeke Bonner's job offer to itinerant laborer Ben Wait involves the stagecoach line and its passengers with the vengeful Sutter clan. The old man blames Ben for the death of his daughter because of the faulty first aid he believes the vagabond administered.
A retiring bookkeeper agrees to help a businessman destroy his factory for the insurance money, but the plot backfires when the owner is killed in a bungled robbery by the bookkeeper's wife's lover. The killer joins the husband and wife on Luke's stagecoach for their trip to San Francisco and tries to steal the five thousand dollars the bookkeeper received as a retirement gift en route.
Matt Dexter, an Irish drifter witnesses a murder but flees town because he doesn't want to get involved. Two of the gunman's cronies decide not to risk his return and ride out after the old man to kill him. Dexter saves Davey Kane's life by killing a rattlesnake about to strike. In return the young man agrees to smuggle food to Matt while he hides from his would-be assailants.
Ralph Barnes, a retired army officer, has one last military mission to perform - delivery of top secret military papers - and he hopes to use his honeymoon as his cover. He is pursued by outlaws who are trying to relieve him of the documents. When the stagecoach stops at Halfway House with the Barnes's on board, Luke makes a disquieting discovery - all the guns in the armory have been stolen and Barnes fears the gang trying to steal his papers now has the upper hand.
Acting in the capacity of a Deputy Sheriff, Ken Rawlins fires at outlaws attempting a bank robbery and accidentally kills his brother who was a member of the gang. Distraught, Ken turns in his badge and heads west, finding work at Halfway House as a handyman. While working for Zeke he bumps into a pair of shady characters from his less than honest past.
When their attempt to steal a herd of cavalry remounts fails, two saddle tramps recruit a pair of outlaws to assist them in another attempt. Their plan is to kill the army officers bringing the money to buy the horses and to force Simon and Luke to assist them by holding Davey as hostage. Simon devises a desperate plan to rescue Davey from the outlaws.
A notorious outlaw gang holes up at a stagecoach relay station to hide from the posse chasing them after they steal a payroll and kill the express agent. The gang captures the stagecoach driven by Luke Perry and Simon Kane and hold Davey, a U.S. Senator, his pretty daughter, and a jewelry drummer hostage.
One of the passengers on Simon Kane's stagecoach is a U.S. Army colonel recalled to Washington to face charges of excessive force against Mexicans living in California. A band of bandits aren't willing to let military justice take it's course and plan to capture the stagecoach, abduct the officer and administer their own kind of retribution without the bother of a trial.
Luke and his passengers find a severely wounded cavalry soldier besides the road. While Luke treats the wound, Brewster makes an amazing discovery - four boxes of gold coins worth nearly two hundred thousand dollars. While waiting to the wounded trooper to recover sufficiently to travel, the small group is beset by outcast Indians who want to steal their food and horses.
Wanted gunman Pierce Martin comes to the stagecoach line, looking for the man he calls his only friend, the local minister. Pierce says he's tired of being forced to kill, but he may have to again, as a posse forms to hunt him down, and the minister is torn between his loyalty to Pierce and to the town he's been serving.
Cole Eldredge, recently released from prison, is framed for train robbery and murder by two of his former friends. Luke Perry convinces Ruby, Cole's fiancee, that he can help Cole if she can take him to where the ex-convict is hiding from the posse who is pursuing him. When Ruby finds Luke's U.S. Marshal's badge in his saddle bags, she decides that Perry has lied to her about being Cole's friend.
Luke Perry is assigned to deliver a Gatling gun to a distant army post. Colonel Martinez discovers that Luke's stagecoach will not have a cavalry escort and determine to steal the gun and force the young driver to deliver it to Juarez's forces fighting Emperor Maximilian. When the American mercenaries assisting Martinez learn that Maximilian has been overthrown they decide to make use of the Gatling's firepower to rob an express office.
Upon arriving in Tucson to visit his brother, Luke Perry learns that the young man fled town when he was falsely accused of murder. Although the true culprit was soon captured by the army, wanted posters offering a large reward - dead or alive - have been sent out to every corner of Arizona and ruthless bounty hunters are still searching the desert for fugitive.
Emily Prince, a pretty blonde new to the Wyoming Territory, takes the stagecoach to Halfway House expecting to meet her fiancée. Instead she makes the acquaintance of a ruthless range detective who has been hired to drive out or kill homesteaders - like her future husband. Simon and Davey Kane decide to help the young couple fight the murderous gunslinger.
While attempting to open up a stagecoach route to a northern Army fort, Luke, Simon and Davey are beset by troubles on their initial trip. The men discover that one of the passengers is not only wanted for murder but is running guns to the Indians. When the coach arrives at a relay station, they discover their fresh horses have been run off and the cavalry patrol promised to provide protection for the army payroll has been wiped out by Cheyenne warriors.
Jaime and Angela Toreno, two teenagers recently arrived from Spain, ride with Simon and Davey Kane to the open range to meet their father who has been herding sheep in the area for the past seven years. When Simon discovers the elderly immigrant has been murdered, he assumes it's the work of hired guns employed to drive the sheep off the range and sets a trap for the killers.
Luke, Davey, and their passengers,a gambler, a preacher, and a snobbish Easterner, along with a disgraced former lawman riding shotgun are attacked at a relay station by a band of renegade Indians led by a former Army captain who has turned into a raider and killer and is known for not leaving any victims alive.