John Grainger and his grandchildren move to Shiloh after he purchases the ranch from Judge Garth. Besides developing a relationship with his new employees, Grainger is faced with a neighbor who blames him for the loss of her husband. Her and her ambitious foreman try to force him off the ranch.
Lemoine Carlson and a ranch hand deliver 50 head of cattle to Grainger for Lemoine's dad. When five head are found missing the next day, The Virginian feels responsible and leaves Shiloh to track them down. He finds them near Delphi but has to solve the mystery of who stole them. He runs into an old female friend with a checkered past who had saved his life. She unknowingly has ties to the rustlers and a murder The Virginian is accused of committing.
A trio of Indians are caught stealing Shiloh cattle. They are a husband and wife with an adopted girl who is really a white girl. The girl is not returned to the reservation and they attempt to find her original parents. In the mean time the girl is reluctantly learning life in the white world and is enticed to return to her Indian life and friends.
After a trip to deliver horses to Colorado, Trampas decides to stay and visit an old friend living nearby. Trampas arrives at his friend's home in time for the funeral of his friend who was shot. While paying respects to his friend's sister and her husband, the sheriff, Trampas senses that there are questions to be answered even though his judgment and others indicate he should go home.
Jake who can neither speak or hear runs away after accidentally killing a man in a saloon. He lands at Shiloh ranch where his extreme strength allows him to become a valued hand in spite of his handicaps. Stace, who learns Jake cannot read or write as well, decides to help him develop the ability to communicate via reading and writing. When Jake stumbles into other problems on the ranch, Stace is forced to help.
Trampas stumbles into the yard of the Crayton family with a head injury and collapses. The daughter, Sarah, takes an interest in Trampas and helps with his recovery but Trampas has amnesia and is suspected to have robbed the stage where he was actually a passenger and hurt. His situation is complicated by a crooked deputy who wants to pin the stage robbery and murders on Trampas.
Charlie Ryan finds himself helping Stace in a fight in Medicine Bow and wins the gratitude of Stace and his sister Elizabeth. Charlie and Elizabeth become good friends causing Stace to worry as he has concerns about Charlie. When they learn Charlie is wanted, Elizabeth provides support and enlists her grandfather's help due to her belief Charlie has to be innocent. In the meantime Stace continues to search for the truth.
The sheriff suspects Ed Wells, a close friend of Trampas, of a robbery and murder as the evidence points to him. After a witness who can give him an alibi dies, Ed and his wife admit that it was her brother Willy who was probably involved but Willy skips town. Trampas decides to help track down Willy but comes to realize other problems are making his task very dangerous.
Marjorie Hammond arrives in Medicine Bow as a teenage girl smitten with dime novels about the west and meets a man like the hero, Dead Eye Dick, in The Virginian. Detecting her interests The Virginian tries to aim them toward Bob Foley who is her age and likes her but as an aspiring attorney, he doesn't measure up to The Viriginan in her eyes. The Virginian tries to enlist the help of everyone to re-target Margorie's interests with limited and comical results.
While helping his friend Wesley Hedges sell his horses, The Virginian's friend falls for a beautiful faro dealer, Alma Wilson. Alma is the ex-wife of an escaped outlaw whose brother has come for Alma and kills Wesley for the money from the sale of his horses. The Virginian rides with the posse to find the killer and when they are forced to turn back he continues the hunt on his own into the outlaw's hangout.
A wild white stallion draws the attention of Elizabeth who convinces her grandfather to buy it. Against his wishes, she tames and breaks the stallion when Trampas is unable to. Her and the stallion become inseparable but a problem occurs.
The Virginian is remitting the proceeds from a horse sale back to Shiloh at an express office in Texas when the office is robbed. Having a receipt for his money, he is allowed to leave. During the return trip he meets Linda Valence on the stage coach and they develop a close relationship. Linda reveals she has become involved in something that scares her and asks The Virginian for advice. He finds himself involved in a deadly mystery clouded by her changing story.
Jim Boyer Sr. decides to return to his wife and son Jim Jr. after deserting them and having no success in his endeavors. Jim is an extremely capable man but impatient to succeed and feels luck goes against him. He sees The Virginian as a rival for the position he wants as well as his wife and son. His lack of attention to detail creates problems as his family warms up to him.
Howie Sheppard is a natural cowhand working at Shiloh. He has fallen for the spoiled daughter, Donna Maguire, of a successful Medicine Bow store owner. They decide to marry and Howie opens a saddle and tack shop. However, Howie feels the urge to return to the open life of a cowhand while working in his shop. A decision to enter a poker game creates complications for him and his new wife.
While gathering supplies for a cattle drive to Shiloh, Stacey is held up and in the ensuing gunfight kills the robber. He returns the body to the family where the sister is understanding but warns Stacey to leave as their younger brother, Toby, will want revenge. Toby leaves to track down Stacey and joins the Shiloh cattle drive to look for his brother's killer. He and Stacey develop a friendship until events bring the truth out.
Sue Ann MacRae has lived as a poor farmer's daughter all of her life and wants to experience the other things life has to offer. She leaves home and lands in Medicine Bow where her father and hopeful boyfriend Joe find her. She finds herself working as a saloon girl and Joe stays to keep an eye on her and hopefully win her love. However, the saloon job creates problems for Joe.
Stacey buys a gold watch that may have belonged to his dead dad. It sets him off on a journey to find the truth about his parent's deaths. He meets an orphaned girl who owned the watch and is curious about her parents who she never knew.
The Virginian arrives in a town to meet Stacey to complete a cattle deal. He finds Stacey in jail convicted of murder and scheduled to hang the next morning. Stacey is believed to have killed the popular doctor of the town after he lost money in a poker game. The Virginian uses his detective skills to uncover the truth and skeletons of the town to prove Stacey is innocent.
A group of men hold up the bank in Mediine Bow resulting in the capture of one man and one wounded in the group of three that escaped. The three men found themselves at Shiloh were they forced the Graingers to get a doctor and take of the wounded member. This resulted in a matching of wits between John Grainger and The Murdoc Kid while the law searched for the bandits.
The Virginian is shot by a rustler while in Texas and is rescued by a rancher and his wife. The couple is having marital problems which The Virginian falls into while healing. The rancher wants The Virginian to stay on as his Foreman until he thinks The Virginian has kidnapped his son. To resolve the problems The Virginian challenges the rancher to ride against him in a grueling gauntlet race planned between two ranches.
Stacey has developed a close relationship with neighbor Kathy Young but her father believes the Grainger family to be in the wrong social class for her. When Elizabeth finds Kathy's father shot in the back and his money stolen, it appears Stacey may have done it as the evidence piles up against him.
Grainger's old friend, Jim Kohler, and his daughter, Melanie, come to Shiloh to visit from Chicago.Upon their arrival at Medicine Bow Melanie meets Trampas and events lead to a serious relationship between them resulting in Trampas asking Melanie to marry him. However, unknown to Trampas Melanie has a dark secret which complicates the relationship.
The Virginian meets the new doctor brought to Medicine Bow by Dr. Spaulding to help with his practice when she arrives at the station. However, unknown to Dr. Spaulding Dr. Pat O'Neill is really Dr. Patricia O'Neill and she encounters resistance from the community being a woman especially after a young man fakes a continuing injury. The Virginian tries to support her while also falling for her charms.
Stacey is shanghaied in Medicine Bow to take the place of a cavalry recruit. An inept officer allows two sergeants to keep up the facade that Stacey is a recruit while putting him through inhumane conditions to keep him quiet. When one of the sergeants is murdered, Stacey is framed for it.
The Virginian is sent to purchase oats for Shiloh from a farmer who happens to be in the middle of a fight between ranchers and homesteaders. After making the deal to purchase the oats, The Virginian finds himself caught in the feud. An over zealous foreman tries to pressure The Virginian to back out of the deal by roughing him up. Further complicating the problem are issues between members of the farmer'f family.
Trampas goes to visit a mother and son he stayed with as a child and finds the son shot to death for attacking a girl and the mother evicted from their farm and gold mine. Trampas does not believe the story fits the friend he knew and as he asks questions the attacks against him push him to uncover the truth.
Trampas has noticed a young lady riding a pinto horse and she catches his eye. He learns she is a member of a new family on a neighboring ranch. He tries to win her interest but finds her reluctant. He learns that her adoptive parents have raised her with biased feelings about her history that affected her socialization. Other factors in Medicine Bow force these issues to be confronted.
John Grainger requests Mrs. Miles, an old childhood friend, to live with the family and teach the grandkids the proper manners and skills he feels they need. Her husband was killed during the Civil War and their Maryland home was burned by union troops. The family and The Virginian come to realize she has an old style attitude on their positions and other goals which push the family in the opposite direction expected by John Grainger.
Claire Bingham arrives in Medicine Bow looking for a brother she was separated from when both were very young. She believes Chuck Larson who is in jail for a stagecoach holdup and murder may be her brother. Sheriff Emmett Ryker takes a strong interest in Claire but does not believe Larson can be her brother. After being shot during an escape from jail, Larson's partners persuade Claire who is a nurse to help him telling her he is her brother.