Three years after the end of the Civil War, Ethan Edwards (John Wayne) rides onto the Texas farm owned by his brother, Aaron (Walter Coy). Aaron is a little wary of Ethan, who has not been seen since the surrender of the Confederate Army, but his children -- Lucy, Ben and Debbie -- are all overjoyed to see him. So is Martha (Dorothy Jordan), Aaron's wife; she and Ethan clearly are in love though they cannot act on it. Ethan brings with him both mementos from his time in the Confederate Army and newly minted Northern money from a recently robbed train. Aaron agrees to hide the money for Ethan and tells him he is free to stay as long as he likes. Ethan knows his welcome is tenuous, however, and after everyone else goes to bed, sits alone on the porch.
The next morning, the Reverend Captain Samuel Clayton (Ward Bond), the area's minister and captain of the Texas Rangers, comes with a posse to the farm. Someone has run off Lars Jorgensen's (John Qualen) cattle. Clayton deputizes Aaron and his adopted part-Indian son, Marty (Jeffrey Hunter) to join the Rangers' posse. A racist, Ethan is unhappy about Marty's presence at Aaron's farm, even though Ethan is the one who found him abandoned as an infant. Ethan tells Aaron he is not to go but instead to stay close to home in case the cattle rustling was in fact a diversionary ploy by aggressive Native Americans. Clayton is glad to see his former compatriot in the Confederate Army but also mentions that Ethan matches the description of a lot of wanted criminals. Ethan agrees to go with the Rangers to search for the cattle but refuses to swear an oath to the state of Texas, believing that his oath to the Confederacy is sufficient.
Marty tries to share his concerns about the trail they are following with Ethan, but Ethan is dismissive because of Marty's biracial heritage. After several hours of riding, the posse finds Jorgensen's cattle slaughtered in the desert. They realize that a band of Comanche Indians have lured them away from their farms. Because Jorgensen's farm is closest, most of the posse rides there. Ethan, Marty and the slightly demented Mose Harper (Hank Worden) ride for Aaron's farm. There they find Aaron, Martha and Ben slaughtered, and Lucy and Debbie missing.
After the funeral, the Rangers go searching for Debbie and Lucy. Ethan and Marty accompany them. Ethan is livid with anger and hatred, demonstrated when the posse finds a partially buried Indian corpse. Ethan shoots the warrior's eyes out to defile the corpse and prevent it from reaching the afterlife. A little later, the posse finds itself surrounded by the Indians. They manage to make it to the other side of the river and fend off the attacking Cochise in a gun battle. However, one of their own men is wounded. Clayton and the others take him back to town. Ethan, Marty and Brad Jorgensen (Harry Carey, Jr.) continue to pursue the Indians to rescue Lucy and Debbie.
Brad and Lucy were a couple, and when he finds the Indians encampment one night, he believes he sees Lucy's distinctive dress. Ethan tells him that he found Lucy's defiled corpse in a canyon when the three men had split up to follow different trails. Insane with rage, Brad charges into the Indian camp on his own and is killed.
Ethan and Marty return to the Jorgensens' ranch. Marty has a tenuous romantic relationship with the Jorgensens' daughter, Laurie (Vera Miles). Mrs. Jorgensen gives Ethan a letter from a trader named Futterman who says he might have information about Debbie. Ethan arranges for Marty to stay with the Jorgensens but Marty follows him anyway, much to Laurie's displeasure. He knows Ethan intends to kill Debbie because she has certainly been married to a Comanche warrior.
Ethan and Marty find Futterman who says he purchased a swatch of Debbie's calico print dress from an Indian band led by a war chief named Scar. Ethan pays Futterman part of the reward. That night, Futterman and two accomplices try to ambush and kill Ethan and Marty for the rest of the money. Instead, Ethan shoots all three men in the back.
By now, the search for Debbie has continued for several years. Marty writes a letter to Laurie detailing his and Ethan's attempts to find Debbie. They have traveled out of Texas into Colorado and parts north. Laurie is outraged to learn that Marty accidentally acquired an Indian bride, Look (Beulah Archuletta) while trying to trade for blankets with a different band of Comanche. Marty tried to drive her away but Ethan finds the situation amusing. When Look learned they were tracking Scar, she abandoned them in the night. They later found her in a Comanche camp that had been slaughtered by the American calvary. Marty and Ethan visited a the local fort where white women who had been with the Comanche. All were deranged but none were Debbie. Laurie swears she will give up on Marty, which delights Charlie McCory, the postman.
Ethan and Marty travel to New Mexico territory, where they find Mose. He has met Figueroa, a merchant who trades with Scar's tribe. Figueroa takes them to meet Scar (Henry Brandon). Scar and Ethan are both annoyed to learn each speaks the other's language. In Scar's tent, Ethan and Marty see Debbie (Natalie Wood), now a teenager. They return to their own camp by a creek. Debbie follows them and tells them to leave her; the Comanche are her people now. Ethan moves to kill Debbie but Marty blocks him. Just then, Scar's warriors attack and Ethan is wounded by a poisoned arrow. He and Marty must flee.
They return to the Jorgensens, where Laurie and Charlie are about to be married. They also learn that they are wanted for Futterman's murder. Charlie and Marty fight over Laurie; although neither man wins, the wedding is called off. Just as Clayton is about to arrest Ethan and Marty, a young calvary officer arrives with Mose. Mose had been captured by Scar's tribe but managed to escape once they came close to the Jorgensens' farm. Clayton organizes his Rangers again and, with Ethan and Marty, they ride out to confront Scar.
Ethan wants to charge into Scar's camp, hoping that Scar will kill Debbie so he doesn't have to. Marty persuades Clayton (who is in charge) to let him sneak into camp and rescue Debbie before the charge. When he does so, he has to keep her from screaming for help. Scar enters the tent but Marty beats him to the draw, killing him. Clayton, Ethan and the Rangers charge into the camp, killing or scattering the Comanche. Ethan finds Scar's body and scalps it. Then he sees Debbie. Knocking Marty aside, he pursues her into a cave. As she cowers, he reaches down and picks her up. Cradling her in his arms, he says, "Let's go home, Debbie."
Ethan and Marty take Debbie back to the Jorgensens' ranch. Lars and Mrs. Jorgensen take her inside, followed by Marty and Laurie. Ethan stands outside, then turns and walks away as the door closes on him.
