Wiley Kane comes to the Ponderosa, along with his sister Annie, offering to work to pay back the debt he feels they owe the Cartwrights from when their father Sam swindled them. Joe tries to teach Annie to read, but Wiley objects to this out of pride. Later Wiley and Annie learn that their father, whom they assumed was dead, is actually locked up in the Virginia City jail.
Several Virginia City citizens appoint Ben as a temporary circuit judge. He soon faces a major test when the bank is robbed clean, and an old safe cracker confesses to the crime - but refuses to tell where he hid the money unless Ben lets him go free.
Don Jose Ortega claims to have a brass box full of Spanish land grants, giving him ownership over most of the area around Virginia City, including the Ponderosa. Although Jose is reluctant to pursue his claim, his nephew, bitter over the loss of land in the Mexican War, would like to claim it back. Making things worse, many others living in the area are determined not to lose their land and will resort to any means to stop the Ortegas' claim.
A judge awards itinerant horse breeder Jim Acton's beloved mare to rancher Sam Whipple. Jim tries to buy her back, but Whipple refuses his offer, after which a fight ensues and Jim kills Whipple in self-defense. The Cartwrights want to bring Jim in to make sure he receives a fair trial, but an ambitious and overzealous deputy doesn't care how he brings him in.
The Cartwrights try to help a religious group that is passing through the Ponderosa, but incur the wrath of the clan's leaders when they come to the defense of one of their members, a young woman whom they accuse of being a witch.
Hoss finds a stagecoach whose passengers have been murdered, except for a little girl who is in a catatonic state due to shock. The Cartwrights take the girl in, hoping to find her relatives, but Hoss is becoming so attached to her he is reluctant to see her go. An uncle of hers is located and arrives in Virginia City, but he has other reasons for being there besides to claim the child.
After falling off a wagon, a dying friend asks Ben to make sure his large estate is given to a relative since he didn't have a will. After posting an ad in a newspaper, several people come forward to claim it.
The Cartwrights are fully aware that Virginia City's new minister is a former gunfighter. But when one of the Ponderosa's ranch hands recognizes him as the man who killed his twin brother, he tries to goad him into a duel.
While hunting cougar, Joe and Hoss find a young woman unconscious and bring her to the Ponderosa. The girl was abandoned in the wilderness by the wagon train she was traveling with because she is clairvoyant and sees bad events before they happen, and they thus think she is a witch. While recuperating, she predicts a future misfortune for Little Joe.
Hoss catches young Billy Penn working with rustlers, but because Billy stops another member of the gang from shooting him, he doesn't tell the boy's father. Billy is embarrassed and bored by his father's hog farm and yearns for a better and more exciting life. But it won't be so easy breaking away from the rustling gang either.
Ben is appointed temporary sheriff after Sheriff Coffee is injured while bringing in one of the Lassiter boys, who has been sentenced to hang. Elizabeth Lassiter, bitter ever since the death of her husband and loss of her ranch, has turned her sons and her foreman into outlaws, and is now threatening to kidnap one Virginia City resident a day and kill them unless her son is freed. Little Joe becomes the third one taken hostage.
Hoss brings young Skeeter Dexter to live at the Ponderosa after his brutal stepfather leaves the area. Skeeter, a boy with a natural affinity for animals, has had no luck with his home life: his mother is bitter and destitute and has blamed him ever since his father abandoned her.
Little Michael Thorpe's father is accidentally shot and gravely injured. Believing that only God can save his father, and told by his Indian ranch hand that God lives on a mountain, Michael wanders off onto that mountain, and finds an old hermit who he thus thinks is God.
Hoss finds a young Indian who's been left to die by his tribe because he is lame. He is brought to the Ponderosa, where the doctor is able to heal his leg so he can walk again. Hoss tries to teach him to overcome his hostility to the white man as well.
If the Pony Express is to survive the growing Indian problem must be addressed. When things get out of hand, it is Ben Cartwright who steps in to save the life of the Indian Chiefs son and secure a peace treaty.
A band of rowdy young punks accidentally kill a deputy in a barroom brawl. With Sheriff Coffee out of town, the mayor sends for legendary peace officer Wes Dunn to take his place temporarily and track down the gang. But it soon becomes apparent that Dunn is totally ruthless and brutal in the methods he uses to catch them.
Ben's old friend George Norton is a brilliant inventor who has ideas for a new type of bridge. He is also an eccentric who fancies himself as, and dresses as, Emperor of the United States and Protector of Mexico. When Norton encourages Chinese mine workers to stand up for their rights and higher wages, the mine owner petitions to have him committed, and Ben tries to defend him.
Claire Armory comes to Virginia City to live with her brother Carl, an invalid neighbor of the Cartwrights. Carl encourages Claire to see Ben, and soon Claire and Ben fall in love with each other. But Carl is a manipulative man who uses his condition in order to get Claire to do what he wants, and tries to use her now to get money from Ben. Claire struggles with whether or not to break free from her brother and marry Ben.
Ben's cousin Matthew visits the Ponderosa, along with his ward Elizabeth and his son Jamie. Jamie is a spoiled and arrogant brat who constantly insults both his father and the Cartwrights. When Matthew decides to leave Jamie with the Cartwrights while he and Elizabeth visit San Francisco, Ben has his work cut out for him in teaching the young man a lesson in behavior.
Little Joe falls for beautiful young Wendy Daniels, who has arrived in Virginia City to wait for her father, who plans to start a stage and freight line there. Wendy has nothing but the highest praise for her father, but the town banker receives information that Daniels has not told Wendy the truth about his financial situation, a fact which could deeply disappoint the girl.
Against Ben's better judgment, Hoss hires drunken Will Smith as a ranch hand on the Ponderosa, hoping to straighten him out. It doesn't work out; he is soon fired for drinking on the job. Then Hoss discovers that Smith is actually a famous poet, William Warlock Evans. He determines to help turn Evans around to his former self.