Set in 1917 California, just before the entry of the United States into World War I, twin brothers Cal (James Dean) and Aron (Richard Davalos) Trask vie for the affection of their father Adam (Raymond Massey), although it is clear that Aron is considered the "good" son and Cal the "bad" one. When Adam loses thousands of dollars in a failed attempt to ship lettuce to New York, Cal enters the bean-growing business, speculating that the price of beans will skyrocket during the war. As the war drags on, Cal's speculation translates into a small fortune. Cal decides to give the money to his father to help recoup his loss. However, things don't go the way Cal hopes. The result is tragedy for all three of them.

East of Eden is loosely based on the second half of John Steinbeck's novel East of Eden (1952). The novel was adapted for the movie by American screenwriter Paul Osborn. A second adaptation of the novel, also titled East of Eden (1981), was released as a three-episode TV miniseries in 1981. A third adaptation, also titled East of Eden, is in the planning stages, but details are not yet available.

The title comes from the Bible: "Cain rose up against his brother Abel and slew him" (Genesis 4:8, King James Version); "And Cain went away and dwelled in the land of Nod, on the east of Eden" (4:16). In essence, the story of Cal and Aron is a retelling of the story of Cain and Abel.

In northern California, the Santa Lucia Mountains, dark and brooding, stand like a wall between the peaceful agricultural town of Salinas and the rough and tumble fishing port of Monterrey, fifteen miles away. Cal, Aron, and their father live in Salinas. Cal and Aron's mother Kate (Jo Van Fleet) lives in Monterrey.

Cal briefly explains to Adam that he met some guy in the bar but doesn't know his name. He said that he worked on the ranch when Kate was still with his father and that he knew where she was now.

As the troop train leaves the station carrying Aron on his way to enlist in the army, Adam collapses in Cal's arms. The doctor diagnoses a stroke, leaving Adam totally paralyzed on his left side and partially paralyzed on the right, and will say only that he could live for another year but that he could die that very night. Sheriff Sam (Burl Ives) suggests that Cal, like Cain, should go away someplace. Abra (Julie Harris) and Cal go into Adam's room and, after kicking out a rather obnoxious nurse, Cal attempts to talk to him but gets no response. Rejected once again, Cal leaves the room. Alone with Adam, Abra starts talking at him, telling him how Cal has lived all his life feeling unloved. She begs him to ask Cal for something, some small sign to make him feel loved and needed, but Abra gets no response. She leaves the room and tries to convince Cal to go back in and try once more to talk to his father. Cal re-enters the room, leaving Abra in the hall to find something for the nurse to read. Abra then goes in Adam's room and finds Cal kneeling on the floor beside his bed, talking to him about choices. When the obnoxious nurse sticks her head in the room to ask about coffee, Cal bellows at her, "Get out!" Abra notices that Adam's lips are trying to move. "Cal", he whispers, "do something for me. That nurse...can't stand her...get rid of her." He then whispers into Cal's ear, "Don't get anybody else...you stay...you take care of me." Finally feeling wanted, Cal walks over to the door, kisses Abra, takes a chair, and goes to sit next to Adam's bedside. In the final scene, Abra exits the room, leaving Cal and his father to sit together.

Those who have both seen the movie and read the book say, as do most people when comparing a movie to the novel on which it is based, that the book better fleshes out the main characters and provides more background to the story, while the movie frequently eliminates characters, introduces new characters, and changes the focus of the story. This is particularly true when comparing the book version of East of Eden to the movie. The book is an epic, telling a much longer story and spanning many generations prior to the birth of Caleb and Aron, whereas the movie focuses on one character, Cal Trask, and his alienated relationship with his father. However, the movie does adhere closely to the fraction of the story it tells from the novel.

Dean had major roles in only three movies, East of Eden, Rebel Without a Cause (1955), and Giant (1956). Only East of Eden was released while Dean was still alive. Dean was killed on 30 September 1955 while driving his Porsche Spyder near Cholame, California. He collided with another car and was killed almost instantaneously.