A racist and his henchmen steal a Gatling gun, with plans to massacre everyone - including the Cartwrights - involved in a peace treaty signing between the U.S. Army and the Paitues in Virginia City. The man's hope is that the tragedy will spark another war and eventually lead to the genocide of all Native Americans.
The Cartwrights are about to start a major cattle drive with other ranchers. It has been decided that Ben's foreman will be trail boss on the drive. Weatherby, a fellow rancher who is also with Ben, has agreed to have Kelly as trail boss, until he finds out that Kelly was previously on a cattle drive with him, and fired him for drinking. Weatherby also suggests that his younger wrangler take the job as trail boss, and a conflict is started between both Ben's foreman and Weatherby's wrangler.
Ben's new horse throws him down a steep slope, injuring his back. Joe tries to round up some help, but the settlers in the valley live in fear of the devious owner and his hired help. Joe goes for help from a man named Thornton, but he is wounded by the lowlife cowboys, and has no choice but to ask them for help. A very imaginitive and visually creative dream Ben has of Joe calling out to him and falling beside him, before waking up and realizes he has just had a terrifying nightmare.
On the trail, Joe witnesses a woman kill a man, but the woman rides away before he can positively identify her. He rides into the nearest town, Black River and reports the crime to Sheriff Gideon Yates, and the two ride out to find clues. They find a handkerchief embroidered with the letter "L". Sheriff Yates knows who the killer is, his wife Lydia. She married him before she got a legal divorce from her first husband, Loomis, and killed him to silence him. Gideon tries to coax Joe out of town, but he recognizes Lydia's picture in a photographer's window. When Joe refuses to leave, Gideon tries to shoot him down in cold blood and orders a manhunt against him. Joe's only hope is a Mexican stable boy, who saw Gideon shoot him, and ultimately Joe and Gideon have one of the most memorable confrontations in the series' history.
A man called Davis has shot Colonel Clayton and escapes on horseback. Joe and Ben join the posse that sets out to find Davis. Ben and Joe volunteer to cross the desert. Ben and Joe find Davis hold up at a water hole, when Indians attack and Ben is wounded in the leg, and steal the horses. Joe unties Davis, who tends to a wounded Ben, who is suspicious that Davis will try to escape. After playing a game of cat and mouse, Ben and Davis come to an agreement: survival. Joe makes the decision to cross the desert on foot, while Ben and Davis are at the water hole, both men in need of medical help and justice.
The Weary Willies are hippie-like former Civil War veterans who are now drifters and live off the land. Despite protests from fellow ranchers and the people of Virginia City, Ben allows the traveling band to stay at the Ponderosa. The real trouble begins when a teen-aged girl is raped and the Willies are blamed.