In 1832, Jim Deakins (Kirk Douglas) is traveling in the wilderness when he encounters an initially hostile Boone Caudill (Dewey Martin). However, they soon become good friends. They head to the Missouri River in search of Boone's uncle, Zeb Calloway (Arthur Hunnicutt). They find him when they are tossed in jail for brawling with fur traders of the Missouri River Company. When 'Frenchy' Jourdonnais (Steven Geray) comes to bail Zeb out, Zeb talks him into paying for Jim and Boone too.
The two men join an expedition organized by Zeb and Frenchy to travel 2000 miles up the river to trade with the Blackfoot Indians, in competition with the Missouri Company. Zeb has brought along Teal Eye (Elizabeth Threatt), a pretty Blackfoot woman Zeb found several years before after she had escaped from an enemy tribe. Zeb intends to use her as a hostage, as she is the daughter of a chief. On the journey, they encounter another Blackfoot Zeb knows, Poordevil (Hank Worden); they take him along. Later, Teal Eye falls into the river and is rescued from rapids by Boone.
The Missouri Company knows about the threat to their monopoly. One day, it makes its move. A party led by Streak (Jim Davis) captures Teal Eye and tries to burn the boat, but Frenchy wakes up before the fire causes much damage. Poordevil tracks the enemy and Zeb and Jim rescue the woman. Later, the expedition puts in at a company trading post and leaves a warning not to interfere. A week later, they repulse an attack by Crow Indians. Jim is separated from the group and shot in the leg. Boone, followed by Teal Eye and Poordevil, finds him, extracts the bullet and waits for his friend to heal. When they rejoin their band, they find Streak trying to buy the boat and the goods on it. Jim compares the bullet dug out of his leg with one of Streak's and finds them to be the same. Streak and his men are killed in the ensuing shootout.
The expedition reaches the Blackfeet and begins trading. Teal Eye tells a very disappointed Jim that she loves him... like a brother. Boone follows her back to her teepee. When he emerges much later, he is surprised to find out he is now married. However, Teal Eye makes him buy her from her father, so that he can leave any time he wants to. With winter coming on, the men begin the long return trip. However, Boone changes his mind and decides to stay with Teal Eye.