Dr. McPheeters decides to move west with his son Jaimie. But Jaimie falls overboard from the riverboat they are traveling on and is presumed drowned. Actually, he comes ashore, and is taken by three scoundrels who plan to sell him, along with a young woman who they have also kidnapped after killing her aunt and uncle.
When a troublemaker on the wagon train kills an Indian, the tribe wants revenge and demands that wagonmaster Buck Coulter hand over the killer to them for punishment. Coulter must make a decision whether to turn the man over to the Indians, where he faces certain death, or refuse the Indians' demands and risk an attack on the wagon train.
A man who temporarily joins the wagon train takes a liking to Jenny, but she takes advantage of the situation in the hope of making Buck jealous. But another man who becomes most jealous is far more dangerous.
The Indians refuse to let the wagon train continue without attack unless a con man who swindled them out of their gold is turned over to them. One passenger wants to push through in spite of this, but Coulter refuses. And Jaimie has befriended the con man.
A girl runs away from a band of buffalo skinners and seeks shelter with the wagon train. The ruthless leader of the skinners demands her return, but Coulter refuses. Then an old nemesis of Doc and Jaimie comes upon the skinners' camp and offers to get the girl for them---and hopes to get his revenge in the process.
When Jaimie finds an old Indian staked out and left for dead, Doc insists on bringing him in and trying to save his life, though Coulter warns him that interfering with tribal custom by doing so could put the lives of everyone on the wagon train at risk.
Coulter meets some old acquaintances from his past, who try to use an old secret to weaken his leadership of the wagon train when the threat of Indian attack compels him to make difficult demands of the other passengers.
Jaimie and a young girl befriend a big, simple-minded man named Angus, who is traveling alone with his sister. Unfortunately Angus, though gentle with children and animals, has a problem controlling his temper and does not know his own strength.
In a lighter episode, Jaimie, stricken with a high fever due to chicken pox, conjures up the story of a sea captain and his converted ship traveling through the West, guided by only the stars at night and his wife's astrological expertise. Unfortunately the captain makes a deal with the unscrupulous Murrel and his cohort Shep which could get him into deep trouble---with the Indians as well as the crooks. Buck Coulter appears for the last time here despite his fate in the previous episode.
When Jaimie encounters a runaway boy, they are both captured and taken to a run-down orphanage where all the boys are shackled together, beaten, and forced to work the fields. Only the female indentured servant of the ruthless headmaster is able to get to Doc and Linc and try to let them know what is going on. Linc Murdock becomes the new wagon train guide beginning with this episode.
A group of miners come to Doc with gold nuggets and offer to show him the location of the mine if he will attend to the pregnant daughter of the camp's leader. When he hesitates, their guns give him no choice in the matter. Jaimie secretly follows him to the camp, where Doc learns that the young woman is four months from giving birth, and that the miners want him to stay with her for at least that long.
A traveling fortune teller plans to pass off Jaimie as the long-missing son of a couple who is offering a large reward for his return. To do this, he convinces Jaimie that he is destined to accidentally kill his own father unless he comes away with him and participates in the fraud.
Jaimie and Linc come across a bounty hunter and his prisoner, a mountain man who he is bringing in to hang. The mountain man talks Jaimie into releasing him with a tall tale of a fortune in gold over the hill.
Doc and Jaimie find a diary in an old wrecked stagecoach, which gives apparent instructions about how to find the way out of the dry valley in which the wagon train is trapped with Linc way overdue to return. Then Jaimie decides to go looking for the mysterious robed figure that is occasionally seen up on the hill. Jaimie, and Doc following after him, discover an amazing secret.
Seeing an old derelict being harassed by thugs, Doc and Jaimie invite the man to join them on the wagon train. The old codger interests Jaimie and the other kids with his stories about past adventures on the frontier. But he doesn't tell anyone that he recognizes the "U.S. Marshal" who stops by with his wounded prisoner as a killer outlaw, because the outlaw knows a secret about the old man that he'd rather not have revealed as well.
When Jaimie stops Piggy Trewblood from hanging himself, he doesn't realize the mess that it all leads to. Piggy hopes to buy back his wife, Zoe Pigalle, who he gambled away for 700 dollars. But his efforts to do this land himself, Linc, and Doc in jail, and Jaimie being held as ransom for the money.
Jaimie finds a baby Arapaho boy near the body of his dead mother, one of many slaughtered by an Army contingent. In spite of Linc's warning that bringing the baby on the wagon train will further aggravate the tribe which is seeking revenge, Jaimie hides him in a wagon. A bigoted member of the train demands that the baby be taken back and left to the elements, but his own wife feels otherwise.
After the wagon train stops an attack on an old European and his nephew, Jaimie is then taken by men who have mistaken him for the boy, who is apparently really a prince who they hope to trade for a very valuable chest.
Doc and Jaimie come across a wounded Army lieutenant, who begs Doc to deliver the pouch he is carrying to Fort Dexter. The pouch contains money to be paid to the Nez Perce for food. But when Doc arrives at the fort, the money is gone from the pouch, and the Indians feel they have been lied to and threaten war. The fort's colonel believes Doc stole the money and sentences him to be executed the next day. Reluctantly, Doc agrees to escape with the prisoner in the adjacent cell his old nemesis Murrel.
Stopping with Jaimie in a dusty old town, Linc meets up with his old flame Maria, whom he had thought was dead. She is now married to a bitter enemy of his, one of three crooked brothers who control the town. Linc also learns that in his last gun battle with him, he cost Maria's husband his right arm, for which he is determined to exact revenge.