The story opens in 1843, New Orleans. Roguish gambler Paul Regret (Stuart Whitman) has a duel with a man over a woman and despite attempting to just try and wound him when he fires at him, Regret kills him. When he discovers that the man is in fact the son of a Louisiana judge, he goes on the run to escape the death penalty. Whilst on a riverboat, he is approached by a mysterious woman named Pilar (Ina Bolin), who has one of her men called Amelung (Michael Ansarra) find out who Regret is. Regret is originally suspicious but Pilar convinces him she is interested in Regret and not his money and they fall for each other.The next morning, Texas Ranger captain Jake Cutter (John Wayne) turns up in his room to arrest him. His assignment is to take him to the Texas Rangers headquarters to be handed over to a Louisiana marshal. Before they depart the boat, Regret wants to say goodbye to Pilar but she's gone. With Jake on horseback and Regret on a slower mule to discourage escape, the two travel across the plains. They come to a ranch that Jake used to own. After his wife died, he decided to sell the ranch to a family. As Jake is approaching the family home,he notices some smoke. The ranch has been attacked by Indians and the entire family have been massacred. After Jake gets him to bury the victims, Regret sees an opportunity to escape. He knocks Jake out with a shovel to the head and takes the horse leaving Jake with the mule.Back at Ranger's headquarters a man, Ed McBain, who was arrested for gun running tells Jake and Major Henry (Bruce Cabot) that he was on his way to a town called Sweetwater to sell the stolen army rifles to a contact that he's never met before. Jake goes undercover and takes the McBain's place as the gunrunner in order to go and meet the contact. He arrives at the hotel in Sweetwater to meet his contact who turns out to be Tully Crow (Lee Marvin). Crow tells Jake that his partial scalping was the act of a Comanche tribe and before he was killed he was saved by a group called the Comancheros - the group he's now working for. Crow searches the wagon for the guns and they are not there. Jake tells Crow that he buried the guns because he wasn't sure if he could trust his contact. The two go on a night out to get to know each other before they make a deal. First they get drunk in a saloon and Crow shoots the place up. Then they go on to a quiet restaurant and decide to join a group of men in a poker game. As they introduce themselves, Jake sees that one of the card players is Paul Regret. Regret looks uneasy and Jake is quick to introduce himself as Ed McBain. They shake hands and Crow appears suspicious of the two men. Jake wins a few hands and Crow becomes increasingly angry that he's losing. Crow accuses Jake and Regret of cheating. Jake tells him he's just drunk and tries to leave. As he walks away ,Crow pulls his gun and Jake whips around and shoots him. Jake thanks Regret for not giving his real identity away but he tells Regret he isn't off the hook. Regret is still a wanted man and Jake arrests him again. He takes him out to the desert and gets him to dig up the rifles that he'd buried.They arrive at a ranch where a family lives that Jake knows. The ranch is occupied by the Texas Rangers who are on a Comanche patrol. The major and the patrol pull out and leave Jake and Regret and a couple of injured Rangers behind. Regret and the Rangers share a meal inside with the rancher and his son while his pregnant wife rests in bed. The wife sees Comanches coming across the river to attack the ranch. Despite been outnumbered, Jake, Regret and the few rangers that are still there including the young Tobe (Patrick Wayne ,and the rancher and son do their best to fend them off. During the shootout, Regret gets away on an available Indian pony. Jake thinks he's escaped his custody again. Regret reappears with Major Henry and the rest of the Rangers to take care of the Comanches. Feeling like they owe Regret something, Jake asks the Major if he can have a word with the judge about a reprieve for Regret for helping to save their lives. Inside the cabin, the rancher's wife gives birth and the rancher suggests naming the baby Cutter after Jake. But Jake refuses and suggests the boy should be named after Regret for his good deed.Jake and Regret eventually arrive at the judge's office and Regret is told that the Rangers plan to commit perjury in order to prevent him from been sentenced. They make him a Texas Ranger with the understanding that he has actually been one for a couple of years so if anyone asks he couldn't have been in New Orleans for the duel and killing.Jake is assigned to go and track down the Comancheros and he requests that Regret be partnered with him. They wander the desert in a wagon with Tobe following in the distance on horse, ready to report back to the Rangers when they uncover the Comanchero hideout. Jake and Regret eventually attract a group of Comanches. They tell the Comanches that they have rifles for the Comancheros. The Comanches take them to the hideout where Jake and Regret discover a secret society of thieves and murderers. Jake tells them they have rifles for them but the firing pins are missing and they are just a sample of what they can offer. Aemlung, the man from the riverboat who saw Regret, orders that they be taken prisoner and tied up by their wrists. Pilar, the woman from the boat who fell for Regret arrives and instantly recognizes Regret and orders that the two men be cut down. The two of them are put on trial by the wheelchair bound but ruthless leader of the community, Graile (Nememiah Persoff), who is Pilar's father. Because of her personal feelings for Regret, she defends them stating that it would be best to let them live as they can provide them with a continuous supply of guns and also use their skills. Graile agrees and gives Jake and Regret a tour of his home and explains the society that he has created. He invites the Jake and Regret for dinner and they spend the time beforehand scoping out the hideout for a possible escape.As sunset approaches, Tobe is in the desert on his way to get help from the rangers but he is ambushed and killed by two Comanches. At Graile's hideout, Pilar tells Jake and Regret that she will have horses prepared ready for their escape. But Jake has no intention of leaving without arresting Graile and he steals a gun from one of the Comacheros and is ready to confront Graile at dinner. As they sit around the dinner table talking, Pilar tells her father that she plans to go away with Regret but she wants her father to leave as well before the Rangers arrive. Graile says he won't leave his empire that he has built and Jake pulls the gun on him. Aemlung walks in with the dead body of Tobe wrapped up in a blanket. Jake gets Regret to take care of Aemlung with his fists because he doesn't want to fire his gun and signal Graile's men. Regret subdues Aemlung and Graile calls in his huge henchman Gordo. After a struggle with Jake and Regret, Jake knocks Gordo out with the pistol. Regret and Pilar get ready to leave and Jake unwraps the rug to look at the dead body and tells Graile that he's going to take pleasure from watching him hang.Jake, Regret and Pilar get ready in the wagon to sneak out with Graile and Aemlung and Pilar's loyal man Esteban. But as they try to quietly depart, Graile shouts out and his henchmen wake up. The mother of a man who was earlier executed by Graile, runs up to the wagon and stabs Graile in the back with a knife. As Regret drives off, Aemlung jumps from the back of the wagon and is untied by his men. A chase ensues with the Comancheros who kill Esteban and later they run into a group of Comanches who join in. Jake is in the back firing his rifle and throws the cover off the wagon so it is dragging behind them and sets fire to it to stop the pursuit from getting too close. Riders get ahead of the wagon and Regret loses control and the wagon flips over. Jake, Regret and Pilar take cover behind the wagon. The Rangers arrive to rescue them. Pilar sees that her father is dead from the knife wound. Amelung tries to kill Jake but Regret shoots him. The story ends with the Rangers cleaning out the headquarters of the Comancheros. Jake says farewell to Regret who is riding south with Pilar.