When a defiant young brave and his mother turn up at a wagon train stop, the town's female boss won't release needed provisions, to keep the caravan at a standstill. Nothing about the situation is as it seems, including that the mother's hiding a knife to murder the town's most prominent citizen. Wagonmaster Christopher Hale is caught between getting his wagons rolling, keeping his men and the brave from killing each other, and satisfying the town's woman boss one way or another.
Due to orders from Washington to limit costs, Colonel Lathrop denies Chris Hale's request for a military escort for the wagon train as it travels through hostile Indian territory. However, he does order Hale to take the wife of Captain Winters on the train with him. As the only woman at the fort, Nancy Winters is drowning her fear about her husband's safety, and her sorrow over the death of her infant child, in alcohol. Lathrop finds her attitude and behavior distracting to the discipline of his soldiers.
Tough, self-made railroad owner Gus Morgan wants to tunnel his rail line through a mountain. His college-educated brother Ethan, distressed over twenty men who were killed attempting to build the tunnel, wants to find an alternate path up and around the peak. While accompanying the two brothers as they trace Ethan's proposed route, Hale is accidentally wounded when Ethan slips and his gun discharges. The three men are caught in a blizzard, and their horses lost. When Ethan collapses, Gus, unable to carry both men, is faced with a terrible dilemma and makes a decision ...
Duke and Charlie are taken prisoner by servants of Princess Mei Ling, matriarch of a hidden Chinese empire, and forced to work as slaves. Coop, who has some familiarity with the legend of the princess, manages to get himself into her quarters. The princess Ling takes a liking to Coop, as he bears an uncanny resemblance to her late husband, an Irish sea Captain. She makes him an offer, to take her niece as his wife and inherit all of her riches. Coop has to figure out a way to free Duke, Charlie, and the other slaves even though he is coming to admire the princess.
British journalist Robert Harrison Clarke joins the wagon train, along with his Sikh aide, hoping to write a story on the "real" West. Clarke is a pompous and arrogant man who looks down on his fellow wagon train members, and thinks that stories about the West are simply exaggerations. His beliefs will be tested, as the train is taking a new road through Indian country, and the Comanche and Kiowa leaders are vowing to attack if Army officers show up with Hale's group.
Coop accompanies Grace Marshall to visit her sister Myra whom, traumatized by an upbringing by an abusive father, Grace finds living a life of addiction and infidelity for which Grace wrongfully blames husband Vern.
After witnessing a bank holdup, Barnaby is taken hostage by the robbers, outlaws Sam Spicer and Reno Sutton. Sam takes a liking to the boy as he reminds him of himself when Reno first made him a partner. But Reno doesn't trust Barnaby and thinks they should just kill him.
Coop and Rose Pulaski are falling in love with each other, but Rose's brother Sam objects, as he has to every man Rose has wanted to be with. When Coop finally meets Sam face to face, he recognizes him as the leader of a gang that beat and robbed him in Brooklyn a while earlier. Sam tells Coop he is coming west to change his ways, but doesn't tell that two of his confederates have also joined the train.
Eli Bancroft became an outlaw and raised his three sons as such after a town's citizens banded together and under threat forced his entire family to uproot, fearing they would catch their illness. Now, they have robbed Coop, a young couple, and a young widow and her daughter, taking their water, wagons and horses and forcing them all to walk through the desert.
Victor Harp tells Kitty that he has married her while still married to Martha who he must join on the Wagon Train to take to San Francisco for a divorce. He hires former acquaintance and waster Miles Brisbane to pretend to be Kitty's husband so Kitty can go along and Harp will not be discovered as a bigamist. When Harp tells Kitty that he can not leave wealthy Martha, Kitty gives Harp and ultimatum which he mocks and in anger she shoots Harp to death and then flees the wagon train. Martha offers a reward for the return of Kitty and Brisbane pursues her for the reward ...
Years after using her considerable charms to escape from a Confederate prison camp, singer Sandra Cummings joins the wagon train, along with her musical troupe and her daughter Paula. From the time he first sees Sandra, Coop begins acting strangely, starting a relationship with Paula despite Sandra's excessive objections to her daughter seeing any men. Coop's behavior even starts to alienate Duke and others on the wagon train, and Sandra has her troupe members try to beat Coop up. The reasons for the attitudes of both Coop and Sandra are brought to light later.
The Bleecker gang disguised as farmers with several wagons seek Hale's wagon train to join but they actually carry a wagon of weapons and plan to hijack the train and use it and the weapons to rob a nearby fort of gold.
At the beginning of the story Coop and John Cain are brought into Cain's hometown, both very seriously wounded, and with Cain's wife vowing to make sure Coop lives so he can suffer. It all started when Coop, while scouting in the desert, found Cain, dehydrated, delirious, and near death. While recuperating Cain offers to sell shares in the goldmine he's discovered to all others on the wagon train. But after he recovers, he takes back his offer, and Coop, angry for all the disappointed people, goes after him.
Cassie Vance is accused of theft when money and items belonging to a woman on the train that she nursed turn up missing, and especially after another woman recognizes Cassie as having served time in prison for theft when young. This causes her husband to shun her as well.
Canaby, who is unjustly reputed to have led a wagon train to disaster in the desert, becomes unexpectedly part of Hale's train as Hale has some of the same problems Canaby had and the train carries a widow wanting revenge against Canaby.
Young Julie Holland is falling for Michael Malone, a young man haunted by the death of a woman from his past, which he feels guilty about. Meanwhile, the marriage of another young couple, Ben and Beth Mitchell, is strained because of Beth's increasing bitterness toward her husband and her own feeling of unworthiness.
Jed Whitmore, one of three brothers that committed an infamous train robbery, is now town sheriff Frank Lewis but his brother released from prison comes to town with a fellow inmate and a reporter to get paid for the Jed Whitmore story.
Hale's train must take a dangerous desert route due to hostilities which danger grows when spoiled Geneva Balfour starts a fire destroying supplies to get her husband to return east and Hale lies to train members about the danger's extent.
When Hale begins to romance tough, independent freight line operator Kate Crawley, the others begin to fear she will wind up dominating the wagon train, and try to encourage her adoring assistant to better himself so that she'll notice him instead.
After setting a bomb which killed his tyrannical boss, Grover Allen joins the wagon train and heads west with his widowed daughter Della and grandson Jeff. But a detective searching for Allen also joins the train, and he finds his job complicated when he falls for Della.
Everyone wants to help pretty Melanie Craig after her husband is killed in an accident, and several men fight over who will be the one to court and marry her, including Rudd Basham, a father of three boys with all the wrong ideas about how women should be.
Beautiful but shrewd Pearlie Garnet was forced to leave the wagon train after she was found to be a liar, manipulator, and thief who stole from everyone on the train. Now Bill and Duke have come across her again, as the owner of the biggest saloon in a small town. We learn how she managed to achieve that, and who suffered for her success.
Duke and Bill are rescued from Indians by a stranger. He joins the train which is headed to Fort Chacon. Unknown to them he is an Army officer. Members of the train are offered stolen Army supplies creating a problem for the officer.
Wealthy Engel has used psychopathic Harry Diel as a proxy during the Civil War to save Diel from jail but Diel plots on the train as Engel's employee to usurp Engel's business by making himself appear a cuckold to Engel among other wiles.
With Hale gone for supplies, Bill Hawks is in charge of the wagon train, and he threatens to punish Barnaby with a whipping after the boy's pranks get out of line. Feeling humiliated and angry, Barnaby runs away and breaks his leg---twice, the second time very seriously. Bill feels responsible and starts turning to drinking, and hence endangering the train. At the same time, a cynical drunk on the train begins to change in the opposite direction and stops drinking and starts taking more responsibility.
When Coop brings Kim Case to her home town of San Saba, he finds the people there in fear after recent Indian raids, and the nearby Army fort ready to attack. The Army major's adopted son, an old friend of Coop's, is an Indian himself whom Kim has long been in love with, despite the strong opposition of her uncle, whose wife and children were killed by Indians. It is learned that the Sioux have teamed with the Crow and Kiowa to fight in retaliation for massacres led by notorious anti-Indian leader Santiago Quesada.
Duke stops by the town of Stark Bluff looking for a friend and his wife who had formerly been on the wagon train. He finds out that the friend is dead, and his wife has been forced to work for ruthless saloon owner Zeb Stark, who bosses the town, including the judge and sheriff. When Duke tries to help her he is framed for killing a deputy, and Stark uses Duke's life as leverage to force the woman to marry him.
Coop brings Link Cheney to the wagon train after the professional gambler is wounded by sore losers in a game. Link is nursed back to health by Dorthea Gillford, and the two fall in love, but Dorthea hopes Link will quit gambling. A problem arises with Link's old mentor Eucher Jones, who plans for Link to play and lose to his new protégé.
As the wagon train approaches the end of the trail, Hale's crew and passengers deal with birth, death, romance, a clash of different faiths, anger, gambling, a medical emergency, and a cooking contest.