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.
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.
Coop has to escort an ex-marshal and his wife who once shot Coop in the back to the wagon train. In addition he hires three men temporarily who hate the marshal but have more extreme plans for the man without Coop's knowledge.
Hide hunters, hunters who kill buffalo for their hides only, have temporarily joined up with the wagon train. One of their number, Gib Ryker, is a sociopath who enjoys antagonizing young Barnaby West. With the train desperately needing fresh meat, Cooper Smith, along with Barnaby, sets off with the hide hunters to look for buffalo. Along the way Gib continues to bait Barnaby, much to Coop's dismay until Barnaby is forced to defend himself, with disastrous results. Now Barnaby has to face Gib's brother Zach, who's out for revenge.
John Gillman being chased and shot in the leg by a posse escapes via a river. He is found downriver nearly passes out by a young orphan girl Abigail. She takes a liking to him but he tries to rebuff her. Wowever, events cause a change.
Bill accompanies Barnaby to Sam Race's tent city of "entertainers", where a girl from the train that Barnaby likes has taken a job, not as a singer, as she had thought, but as a saloon girl. Bill hopes to keep Barnaby out of trouble with the gambling and con games Race runs, but trouble and humiliation is just what they both find.
Cooper Smith is on his way to the town of Washburn to pick up long awaited mail for the wagon train when he stumbles upon a stagecoach robbery in progress. The very proper Miss Barbara Lindquist is on her way to meet her fiancé, mistakes Coop for one of the robbers and ends up forcing him to help her. Further misadventures see Coop wounded and both he and Barbara struggling to get to back to the wagon train for help. Believing his wound will end his days as a scout, Coop finds himself falling in love with Barbara and she with him. But will their love stand the test ...
Brian Conlin walks into Hale's camp, delirious and dehydrated. After he recovers, he leads Coop to his group of Irish immigrants, whose wagons have broken down, and Hale invites them to join the wagon train. However, having been repeatedly turned away from place after place, most members of Conlin's group are slow to trust anyone or accept help.
Coop falls for a young half-Indian woman wandering alone in the wilderness. He brings her to the wagon train, where Hale discovers she is a survivor of a tribe totally massacred ten years earlier. A sheriff says she has killed two people.
Hale is unable to take everybody on the next phase and has to turn down some of those applying. One is Ben Campbell, an ex-convict who is being hunted by his escaped former partner, who believes Ben turned him in to the law among others.
Spoiled Nancy Styles, claiming to be the daughter of the owner of the company that owns the wagon train, is determined to get to Denver by forcing her way onto it and then Hale makes it clear he plans to bypass the city due to early snow.
A blind man called Sangre has joined the wagon train along with his guide. He is actually Coop's boyhood blood brother Richard Bloodgood, and he openly states his plan to kill Coop. Coop gets very hostile and refuses to discuss it whenever Charlie or Barnaby ask the reason Richard wants to kill him, but they know it has to do with the death of a beautiful woman long ago.
With Hawks ill and Comanches threatening to attack, an Army troop meets up with the wagon train. The Indians appear to greatly outnumber the soldiers, so to give the train hope the troop's lieutenant falsely tells Hale and Coop that there is also a relief column headed their way. Complicating matters even more, a sergeant from the troop recognizes Clay Shelby, a young man on the wagon train traveling with his pregnant wife, as a deserter from back in the Civil War whom he blames for the death of his brother.
Charlie has finally found someone else who shares his dream of man being able to fly, henpecked inventor Hector Heatherton, who has been working on an idea for building a flying machine so Charlie volunteers to build a machine for Hector.