David Sutton takes a job at Shiloh to make up for the work Trampas can't do after being involved in Trampas breaking his leg. He has a hard time fitting in with the other hands while a girl he met earlier tracks him down to help her.
Photographer Dan Sheppard arriving at Shiloh to take pictures of western life finds a neighbor ranch is owned by an old girlfriend. She is in a tug of war between the an oil speculator and the local ranchers afraid of polluted water.
Tim Bradbury wants to recreate the cattle ranch he had in Texas and feels Clay Grainger owes him the help. His son Walt wants to farm instead while his son Mike who works at Shiloh puts the family in financial peril with his gambling.
Elizabeth is blinded by a stagecoach accident. She is found by Ben Oakes who wanted to kill Trampas who had to miss the stage. Ben tries to help her home but becomes lost. After they are found, She is in love with the conflicted Ben.
The Virginian and Trampas are close to the Canadian border delivering cattle and forced to wait at a remote inn for payment. They find the inn managed by an ex-Canadian Louis Boissevain in exile and a his fiancé Suzanne Mayo who scammed Trampas several years earlier for a large amount of money. The Virginian and Trampas find themselves in the midst of an apparent attempt to convince Louis to return to Canada to lead a revolt while Trampas is asked by Suzanne to keep her secret but all is not as it seems.
Shiloh hand Rafe Judson is mistaken for an outlaw as the two men look identical. When Rafe loses an option on a ranch due to a lack of funds, he decides to take advantage of the situation to rob a stagecoach without taking the blame.
Shiloh and its neighbor's cattle herds are threaten by an outbreak of anthrax. A wounded man and woman wanting horses tell Clay the stage with a vaccine was robbed and they are chasing the outlaw gang so The Virginian and David join them.
The Viriginian finds a woman unconscious on a remote mountain trail on the way to visit his friend Jingo. He takes her to Jingo's cabin and they wait for her to recover as no help is available. She wakes up but is slow to communicate and recover her memory. At the same time another visitor arrives with a lame horse asking to stay until his horse can travel again. As the woman recovers she is attracted to The Virginian in a romantic manner but remembers no details.
The Virginian and David are to pick up a herd of horses Shiloh needs for a cattle drive. The horses are stolen from the seller so they must catch and break a new herd but a conflict between a father and his son over his future intervenes.
Clay's old sweetheart Nora and her husband a Major in the Army stop at Shiloh. Nora tries to impress everyone with herself and her down to earth husband. She is willing to put others lives on the line to help her husband win a promotion.
Trampas and David are sent to buy a bull at Durango for Shiloh. The Virginian vouches to Clay that Trampas can be relied on but it is David who finds himself in trouble. He agrees to be engaged to a woman he bumps into on the street.
Frank Hammel known as a gunman arrives on the stage in Medicine Bow shortly after The Virginian arrives in town. When the people of Medicine Bow learn of Hammel's arrival many of the residents with skeletons in their closets believe he is after them. Hammel tells The Virginian who knows Hammel personally that he is waiting for the 2:30 pm stage but the Virginian believes he after someone. One by one Hammel indicates he is not after various citizens of Medicine Bow. However, The Virginian uncovers the truth with a twist.
David kills a man in self-defense on Shiloh who stole his girlfriend. He is forced to stay at Shiloh as the man's father and brother wait for him in Medicine Bow as Trampas who is in charge encounters unusual problems on the ranch.
The Virginian runs into an old friend Bill Burden who is accused of robbery and murder after their meeting. Bill's son, Dan, comes and ask The Virginian to come immediately to Socorro Creek to clear his dad. The Viriginian is delayed a day by Shiloh business but still arrives before the scheduled trial. However, when he arrives at Socorro Creek he finds his friend lynched. The Virginian is determined to learn the truth and Dan wants revenge while Kate still has feelings for the Virginian as he had for her.
After a fight with Trampas, David leaves. He finds himself not only robbed of his clothes and horse by bank robbers but arrested for the robbery himself. Trampas who followed to get him to return, finds himself in the same jail cell.
An orphan who lived with the Graingers in Texas 15 years earlier comes through Medicine Bow. He decides to stay and work for them and is very protective of the Graingers but his years away from them have changed him - in a bad way.
Clay Grainger sends a letter to The Virginian to take on a new hand, Scott Austin, while Clay is in Denver. Scott is the spoiled son of a wealthy self made man who is hoping a summer working at Shiloh will make him a responsible person. Scott is insecure and after several incidents including one involving the thoroughbred colt belonging to Elizabeth,he decides to leave. The Virginain goes after Scott and tries a scheme to change Scott but it has unintended consequences for both of them.
A dispute ends with one man dead, the Sheriff unconscious, and the shooter on the run. The Virginian, Trampas, and David catch the shooter with his family. The softhearted David wants to let the shooter go but The Virginian won't go along.
The daughter, Eileen Linden, of a friend of the Graingers comes to visit the Graingers. Her father has asked her to take a six week hiatus from seeing Peter Bowers who she wants to marry. Her father does not trust him. When Peter follows her and starts working at Shiloh, her and others become entangled in a situation that make none of them happy. Eileen finally comes clean with Clay but other problems surface.
Trampas is sent by stagecoach on a cattle buying trip. At a way station two soldiers and a payroll join the stage and they are told there may be Indian trouble ahead. When the coach stops for rest and water, Trampas finds Jason Adams standing in the river over the dead body of the ferry man from Diablo Crossing where the stage is headed. At Diablo Crossing they find the ferry destroyed and Bud McLister and Marcy McLister who are brother and sister. While repairing the ferry, Trooper Rankin takes a shine to Marcy, they are shot at, and the horses disappear followed by ...
Elizabeth goes missing. Clay and The Virginian ride out to search, soon followed by Trampas and Holly. They find Elizabeth trapped in an abandoned mine, where she had taken refuge during a storm. Another cave-in thwarts efforts to dig her out. Things look bleak until wolves are spotted near the mine, raising the possibility that the animals may have been using a forgotten emergency tunnel as a den. A desperate search for the tunnel ensues.
Claire Garson and her manager Nathaniel E. 'Doc' Watson who are entertainers are hired to have Claire assume the identity of the lost niece of Charles Grainger, Clay's dead brother. Charles was killed in a mine disaster in California and Clay has no knowledge of him other than his death since Charles left Texas. Claire's "entertainment" abilities and honesty, however, interfere with her ability to assume the role.
Luke Nichols arrives at Shiloh searching for Trampas. He and Trampas were cell mates in prison when Trampas was sentenced to hang for a murder he did not commit. They escaped prison together. Trampas was cleared of the murder and Luke escaped to Canada where he waited for Trampas to join him. Bracken, a bounty hunter, traces Luke to Trampas who tries to hide Luke with Widow McCloud but Bracken finds him and blackmails Trampas for Luke's freedom.
The Virginian encounters a stranger, Garrison, on a trip when both are victims of separate robberies. Garrison is very standoffish with everyone but The Virginian finds him a reliable person and hires him at Shiloh. When the foreman at a neighboring ranch is murdered and the owner is shot and robbed, Garrison is thought by the community to be guilty based primarily on his actions. However, The Virginian is not so sure but the case tightens against Garrison.