Having just left St. Joseph, Hale tells everyone there are no Indians when in fact two escaped Comanche captives steal two horses and show up at the wagon trains first stop. The female wants to kill a man there - her cowardly husband.

As the wagon train reaches Fort Pierce it is in dangerous Indian country. Chris is hoping the Army will provide an escort when they leave, but the Colonel refuses due to Army orders. In fact, he wants the lone woman there to leave with the train.

A tough railroad executive and his younger college educated brother are guided by Chris up a mountain to scout a route. When is accidentally shot by the younger brother, the older brother is forced to make a tough decision he may regret.

When Duke and Charlie do not return from a scouting assignment, Chris sends Cooper who has a pretty good idea what lays ahead. The Chinese widow of an Irish Ship Captain wants Coop to carry on her husband's empire.

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 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.

On the train Coop is falling for the sister of the man running a gang who beat and robbed Coop in Hell's Kitchen in Brooklyn. Coop believes the man who says he is going west to change but his goons are still plying their scam on the train.

Eli Bancroft became an outlaw looking for revenge raising his three sons as such after a town's citizens banded together and forced his entire family to uproot, fearing they would catch their illness. Coop and others become his victims.

Kitty Pryer finds herself in a bigamous marriage to Victor Harp who asks her to join him on the wagon train posing as the wife of a friend until he can divorce his wife. However, Victor's change of plans puts Kitty in unique peril.

After escaping from a Confederate prison for being a spy, Sandra Cummings, becomes the lead in a musical troupe in the west. When she joins the wagon train, Cooper Smith takes an interest in her daughter Paula against Sandra's wishes.

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.

While scouting Coop nearly dies after finding a man near death from lack of water who has found a major gold strike. The man decides to let the wagon train share in his windfall but later reneges resulting in disaster for him and Coop.

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.

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.

Julie Holland is falling for Michael Malone, a man haunted by the death of his sister. Meanwhile, the marriage of Ben and Beth Mitchell is strained because of Beth's increasing bitterness toward her husband and her 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 Chris, and try to encourage her adoring assistant to better himself so that she'll notice him instead.

After being fired and setting a bomb which kills his tyrannical boss, Grover Allen joins the wagon train and heads west with his widowed daughter-in-law Della and grandson Jeff. A detective searching for Allen joins the wagon train.

Duke Shannon, arrested by the Cavalry, is charged with criminal negligence as leader of an expedition into the badlands, from which he alone has returned. He must retrace his steps with the Army and one of the victim's father.

Everyone wants to help pretty Melanie Craig after her husband is killed in an accident so four men fight over who will be the one to court and marry her. Also, Rudd Basham, father of three boys, uses the wrong ideas about women to win her.

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.

A strangler is loose in the town of Bedrock so when the wagon train comes through it is joined by a good percentage of the town's population which it becomes apparent includes the strangler.

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 Chris gone Bill is in charge of the train when Barnaby goes overboard in his pranks. After messing with a wagon wheel, Bill orders him to fix it by himself causing Barnaby to break his leg causing a major rift between them.

Kim Case is returning home during Indian wars after schooling in the east although her parents have died. She is anxious to return to the man she loves, Lance Starbuck, who is an Indian raised by an Army Major from a young age.

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.

Barnaby and Charlie talk Chris Hale into hiring legendary mountain man Zebedee Titus as a scout. The nearly 80 year old Zeb's failing eyesight leads to problems including Coop's being captured by the Comanche Zeb couldn't see.

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 as they prepare to separate.