A young woman named Jenny Winters claims to have witnessed a stagecoach robbery which involves one man being killed. After she identifies the culprits as the Logan gang, Ben allows Jenny to stay in protective custody at the Ponderosa. However, the Cartwrights soon learn Jenny is not a very trustworthy person.
Candy is accused of a string of serious crimes, including murder, robbery and arson in Stillwater, and when the Cartwrights come to his defense, the sheriff refuses to cooperate. Even worse: A young boy claims he positively saw the Ponderosa foreman commit those crimes. The Cartwrights work with the boy to jog his memory before an innocent Candy is convicted and sentenced to hang.
When Sheriff Roy Coffee and Ben are subpoenaed to testify in a land sharking trial in San Francisco, Hoss is appointed the acting sheriff of Virginia City. Hoss soon finds plenty of trouble on his hands, namely dealing reluctant bridegroom Hiram Peabody, who wants to get arrested so as to avoid an impending marriage to an undesirable woman (whom has been his pen pal and has never met in person). He also must deal with a smooth-talking salesman who plans to sell shares in a planned resort in Virginia City.
Will Griner is acquitted of a murder after two key witnesses disappeared before the trial. When a bloodthirsty lynch mob comes after him, thinking him to have silenced the witnesses, Griner goes to the Cartwrights for help.
Joe's old friend, Dan Logan, is hired as a range detective to stop a cattle rustling outbreak. While the usual problems arise, Logan's job is jeopardized when a ruthless rancher shoots a suspected rustler in the back and then pins the blame on Logan.
Ben offers moral support to Congressional Medal of Honor recipient Matthew Rush when comes down on his luck. But that's the least of Matthew's problems, for he must also contend with the embittered Nagle clan, who has been transplanted from Georgia after they lost their house and land to Yankees. When the Nagles' daughter, Susan, falls in love with Matthew, she risks much more than just estrangement from her family and, in the process, the Cartwrights become involved.
After Candy shoots and kills armed robber James Campbell in self defense, he learns that he left behind his widow, Lisa, and young son ... and a farm to operate. A remorseful Candy decides to help the young woman out, not knowing that Lisa plans to hire a hit man to kill the Ponderosa's foreman in revenge. However, Lisa learns that Candy had all the qualities that her husband never had and changes her mind, but then they must work together to stop the hit man from completing his mission.
Joe and Candy compete for the attention of pretty Miss Meena Calhoun, who has come to Virginia City with her irascible gold panning father, Luke. While pursuing the young lass, they run into the Potts brothers, a trio of gold claim jumpers who are convinced that Joe and Candy have more than love on their minds.
Joe's friend Wade Turner, a storekeeper who is engaged and has been offered a promotion at work, tries to deal with a devastating brain tumor that leaves him with a paralyzing sensitivity to bright light and will soon render him blind. Turner lets his pride get in the way and decides to put off both his marriage and a surgery that could save his sight, but his attitude could be far more costly when a co-worker tries to rob him in a remote area.
During a long ride back to the Ponderosa, thirsty Hoss and Candy stop at the Sunville saloon where Salty Hubbard, known for his tall tales and practical jokes, tells his cronies that Hoss is the notorious bank robber, Big Jack. The town folk initially scoff at Salty's claim but a series of unfortunate events gives the prevarication a ring of truth and there is talk of a hanging. When a contrite Salty admits to Hoss that he lied to impress his friends, Candy thinks of a way to save both Salty's pride and Hoss' life but, as with most best laid plans, this one goes awry ...
Ben needs to transport three large timber beams but the local freight company won't do it. When a new independent freight hauler is approached for the job, Ben recognizes "Gunny" Riley, a former soldier in the Mexican war, but on the opposite side. Ben finally puts his differences aside and helps Gunny win a lucrative government contract.
Candy quits his job at the Ponderosa after inheriting a fortune from an old Indian friend. He takes a job as vice president of a land promotion firm, unaware that the president is defrauding customers by selling barren desert land in lieu of the fertile farmland he promised them. Candy soon finds out and recruits the Cartwrights to expose the fraud.
Former Ponderosa ranch hand Chris Keller seeks refuge at his old workplace after con artists stalk him for his $67,000 fortune. While at the Ponderosa, he meets a beautiful young woman who has plans of her own for the money.
The daughter of Ben's friend Harry Carlisle, Jennifer, develops a huge crush for the Cartwright patriarch. Ben notes that Jennifer is the same age as oldest son (and long-since departed Adam), but that doesn't matter. It soon does matter when Jennifer's ex-fiancé, a wealthy banker from San Francisco, shows up demanding to take her back ... or else it will be the end of the Ponderosa!
A new school is opened in Virginia City, and one of the students is an angry teen-aged boy named Billy Burgess. After a difficult day at school, Billy angrily wishes that his teacher would die. Sure enough, the teacher is found murdered and Billy is fingered as the suspect. Ben, who has been working to counsel the teen and get at the root of his anger, knows the lad is innocent comes to his aid - even if Billy insists that he killed his teacher.
A ruthless meat packer named Emit Whitney schemes to monopolize the local cattle industry by buying the rail line that is used to transport the cattle to market, then force the cattle farmers to sell at deeply reduced prices. Ben, championing the smaller farmers and knowing that Whitney could drive many of the Cartwrights' friends out of business, devises a plan to drive Whitney out - even if it means he will lose the Ponderosa if his plan fails.
Eleven years after her last stop in Virginia City caused trouble for a young Joe Cartwright, actress Lotta Crabtree returns for another engagement in the Nevada town. This time, it's Hoss who finds himself in the thick of a murder case when he is accused of killing Lotta's co-star during a performance.
While in Los Robles, Mexico, Ben is critically wounded by the town's cruel boss, John Walker. Ben manages to shoot and kill Walker, but now his son - the splitting image of his father - is hellbent on revenge. While Joe tends to his father's care, he tries in vain to embolden the town's residents, who for years have been intimidated into submission by Walker and their cronies. Eventually, Joe's efforts pay off and the Los Robles residents mount a stand against Walker's gang.
In the series' only Easter-themed episode, a Quaker woman convinces Hoss to pose as the Easter bunny for the orphanage. While wearing a rabbit costume, Hoss must try to foil the efforts of a bumbling gang that is plotting to loot the Wells Fargo coach.
Meena Calhoun has gotten engaged to bumbling outlaw Virgil Potts, who is now trying to make an honest living in the livery business. Virgil soon finds himself in a heated rivalry with Joe and Hoss, who have opened up a stable of their own.
A pair of Easterners have read tall tales about the Wild West and come to Virginia City to live out their dream - be bank robbers in the tradition of their heroes. Hoss somehow becomes involved with their adventures.
Alone at the Ponderosa while everyone else is away on a cattle drive, Joe suffers a compound fracture in his left arm when he kicked by a horse spooked by a severe thunderstorm. Joe fights to stay conscious and treat his wounds. When he becomes delirious, he fears that gangrene has infected his arm, leaving Joe with a difficult decision: Amputate, or not amputate?