Russian-Jewish farmer Moshe and his family come to Kansas to try to take advantage of the land. However, their traditions are mocked by the cowboys around, notably a neighboring farm family. One night, one of Moshe's sons and the neighbors get into a fight, and the son is found dead of a broken neck soon afterward. Moshe witnessed the start of the fight but not the actual killing. Under the Mosaic law he treasured, he cannot testify and without his word the farm family is set free. Moshe's second son buys a shotgun and threatens the neighbors with it to compel them to confess, but wastes his powder firing at imaginary targets and is run off the farm. The neighbors then invade Moshe's farm in an attempt to drive him off for good.

An outlaw named Talbot falls in love with the widow of a man he was forced to kill in self-defense. 

Festus Haggen and Newly O'Brien meet an old friend of Festus, Jesse Dillard, an African-American cattle drive cook. Their confab is interrupted by U. S. Marshal Halstead, who has a warrant for Jesse's arrest, charging him with jail break. Jesse goes along peaceably, explaining that he killed his employer for shorting his wages and for a racially motivated flogging. Instead of the normal sentence of six to twelve months, Jesse had been given ten years at hard labor because of his race. Pete Murphy and a few drovers try to rescue Jesse, accidentally shooting the marshal. Dave Carpenter, the owner of the herd and Jesse's boss, rides in with the rest of the drovers to save Jesse from the marshal, who soon dies. Festus is conflicted between his sense of duty and his loyalty to Jesse.

Adam Kimbro, Matt Dillon's mentor as a lawman, is down on his luck. He's a lush, cleaning horse stalls for his next meal. Kimbro takes a short term job as a deputy with Matt, where he must face the kind of man he has become. 

Outlaws led by Dan Whelan come to Dodge City looking to kill Matt Dillon, who is out of town. They attack Newly and Festus, and throw them into jail. The outlaws take over Dodge City, robbing the bank and citizenry. They come to grief when they invite Kitty Russell into a poker game.

Matt Dillon rides wearily into Dodge City after thirty-six hours in the saddle. At the office he can't get to sleep because Festus is so exuberant about everything. In the course of the day Matt fights with a prisoner and is stabbed with a fork. Kitty will not talk to him because duty caused him to miss a picnic. There is a brawl in the Longbranch Saloon. A young boy locks a crotchety old woman in a safe that has no available combination. Finally, Matt takes things into his own hands.

Newly falls in love with a young woman who is dying of leukemia. Later, Doc Adams offers to teach Newly how to become a doctor. 

Just before he's to be hung, stage robber Shadler busts out of jail, by slugging his last rites priest and donning the robes as a disguise. While burglarizing an uninhabited farm, the escapee helps Deputy U.S. Marshal Newly elude hostile lawmen quarantining a nearby outpost struck by a mysterious plague. Newly believes his pursuers are actually a ring of vultures waiting to loot the dying settlement. When Newly heads back to the besieged town, the fake padre insists on riding with him to minister to the dying citizens. Why is the hardened Shadler risking his health and freedom to throw in with law enforcement?

On the run, coming home again proves difficult for two brothers who just want to visit their sick ma. With a desperate and wanted friend along, they feel forced to make some choices they may soon come to regret. 

A very short man rides in on a Giant Horse into Dodge and offers $50 to any man who will take care of him from midnight to dawn tonight, the first light of the full moon, when he will turn into a "Were-Elephant."

Tuck Frye loves to gamble and loves to brag on his fast horse. Festus realizes his priorities are mixed up and he devises a scheme he hopes will get Tuck to give more attention to his wife.

Outlaw gang leader Jude Bonner seeks to force Matt to try and keep his condemned brother from hanging by kidnapping Kitty, brutally abusing and threatening to kill her.

Killer Jay Wrecken is shot dead by Kitty and another man, at the same time, and now the dead man's brother is methodically murdering everyone connected to the incident.

Farm owner Clarabelle Callahan has absolute rights to the water supply in her area. Rather than negotiate with Clarabelle, rancher Lamoor Underwood turns to hatred and violence by bringing in a gunslinger, Dick Shaw. Unknown to either side, farm hand Pete Brown is the noted gunfighter John Jobson and represents a deadly equalizer for Clarabelle.

A grizzly old man, Bodie Tatum, finds out that he only has days to live. His final wish is to be reunited with the family he abandoned years ago. 

When a family man lawfully kills a murderous outlaw by shooting him in the back, some people in town start to physically abuse him. 

Festus heads to Abilene to bring a woman $11 left over from the sale of her things after her father's death, and finds time to teach 2 little boys a lesson along the way. 

When Danny Stalcup, a young member of a gang on the run, is mortally wounded in a fall, Doc Adams is kidnapped, along with Festus, and forced to help. 

Matt runs into an old flame named Sarah that now runs a one woman saloon for bandits out in the desert. Matt will have to pass as a villain in order to save Sarah's reputation as a trusted confidante. 

Dan Shay, a retired Cavalry Sergeant, comes face-to-face with his past as he meets a small Indian boy whose father was massacred in a US Cavalry raid. 

Musgrove spent five years in prison after Ira Spratt turned him in as an army deserter. Now out of prison, Musgrove captures the craven wife beater Spratt and takes him to Dodge City to kill him. In the gun play, Festus and Newly are wounded, and Spratt escapes. He hides in Gideon's barn and again escapes when Musgrove arrives. Musgrove then takes Gideon hostage, threatening to kill him if the townsfolk of Dodge City do not bring him Spratt.

A faith healer shows up in Dodge City and is challenged by the skeptics, including Doc. 

The outlaws catch up with Matt Dillon and the two orphans, Tuttle and Hannah, at the rough mining town. Matt and the children make their escape on the raft, along with the pair of thieves, Pierre and Paulette. As the outlaws ride hell-for-leather along the Rogue River bank, the escapees continue their whitewater rafting journey.

In the Oregon wilderness Matt Dillon escapes with a prisoner from a band of bank robbers led by Charley Utter. They kill the prisoner but continue to pursue Matt for the $24,000 bank loot he has recovered from them. Matt later encounters two runaway orphans, Tuttle and Hannah Kincaid, who are floating down the Rogue River. At a rough mining town, Matt and the children encounter a thief, Pierre, and his partner in crime, Paulette