The Chosen begins in 1944 Brooklyn, as fifteen-year-old Reuven Malter preparing to play a baseball game with his own modern orthodox school against another ultra-orthodox school. The school arrives and it is apparent that the only kid on the other team that can play well is Danny Saunders, the son of one of the many ultra-orthodox rabbis in the area. As the game progresses, the modern-orthodox school is winning against the ultra-orthodox school. In the last inning, Reuven pitches, and when Danny gets up to the plate, he hits the ball at Reuven's eye, and his glasses jab into his eye. Reuven is rushed to the hospital as his team loses. At the hospital, Danny comes in an attempt to apologize, but Reuven is still livid at Danny, and he rejects his attempts, which angers Reuven's father. Danny comes a second time, and Reuven forgives him. Reuven then learns that Danny possesses a photographic memory, yet his fanatically religious father only lets him study the talmud. Danny tells Reuven that despite the fact that his father only lets him study talmud, he sneaks to the library in order to read books on science and literature. He also tells Reuven that a man recommends books for him to read. Reuven and Danny reveal to each other that they have no desire to fulfill the professions that their fathers have set for them. Reuven does not want to be a professor but a rabbi, and Danny does not want to be a rabbi but a psychologist. Reuven learns that the man who has been recommending books to Danny is actually his father, who teaches talmud at Reuven's school. Reuven returns to his apartment after promising to visit Danny over the Sabbath.
Over Friday night dinner, Reuven's father explains to Reuven that only once in a generation a mind like Danny's is born and that Danny must use his brain for secular literature.
The next day, Reuven goes to Danny's family synagogue where he witnesses a discussion between Danny and his father which spans over the entire talmud. After the Sabbath ended, Danny reveals to Reuven that his father only talks to him when they study talmud together. The two boys also reveal that they will be attending the same university, much to Reuven's delight. That Sunday, Danny, and Reuven meet at the library, where Danny reveals his fascination with the human mind and his desire to study the works of Sigmund Freud. He is also learning German and the history of Hassidut (Danny's family's branch of ultra-orthodoxy.)
The next week, Reuven goes to the Saunders house a second time to study talmud with Danny and his father. As Danny is going to get tea, Rabbi Saunders reveals to Reuven that he knows about Danny's visits to the library, but that he will do nothing about it because he must let Danny go. He also tells Reuven that he can not speak with Danny. That summer Danny begins to study Freud with increasing success. The coming year is dominated by America's victory in World War Two, and the death of Franklin Delano Roosevelt, which brings grief to the Malters. In addition, news of the Holocaust reaches American soil, which sends all the characters, especially Rabbi Saunders, into a state of depression. During the summer of that year, Reuven's father suffers a heart attack, which prompts Reuven to stay in the Saunders house. At one meal, Reuven suggests the need to establish a Jewish state, which sends Rabbi Saunders into a fierce tirade against Zionism.
The next year Danny and Reuven enter college, at the Samson Raphael Hirsch College and Seminary. Danny is miserable because the psychology department at the university is only experimental psychology (which upsets Danny as he does not have a natural aptitude in mathematics like Reuven does), and does not tolerate the writings of Sigmund Freud. Eventually, Danny talks to his professor, Nathan Appleman, who tells him that he should attempt a doctorate in psychology. At some point in that year, Reuven tells his father that he will become a rabbi, not a professor. Reuven's father tells his son that he would have been a great professor, but he will also be a great rabbi and that he is happy about his son's choice. Later in the year, Reuven's father gives a speech about Zionism, which leads Rabbi Saunders to excommunicate Reuven from the Saunders family, Danny in particular. Reuven does not cope well without his best friend and his grades begin to suffer. Soon afterward Reuven's father has a crippling heart attack leading to his father being hospitalized for several weeks. Reuven copes with his father's absence by studying the talmud with greater intensity, eventually rising to the point that he has mastered a very complicated section of the talmud. Just as the violence in Palestine comes to an end (the 1948-49 Arab-Israeli war) and Reuven's father has recovered from his heart attack, Danny is allowed to reconcile his friendship with Reuven.
As the years pass, Danny's father still continues to remain silent. At the same time, Danny reveals to Reuven that he will not take his father's place. Instead, he will apply to graduate school and achieve his doctorate in clinical psychology, and his younger brother, Levi, will most likely assume the leadership of the family dynasty. He applies to Harvard, Columbia, and Berkeley. He gets into all three universities, but he notes that his father must have seen the letters and he didn't say anything to him.
On Passover of Danny and Reuven's senior year of college, Reuven is invited to Danny's house for a meeting with Danny, and Rabbi Saunders. Rabbi Saunders tells Reuven that he knows that Danny will not be assuming the rabbinate. He states that he both saw the letters, and also sees the look in Danny's eyes. He then explains why he raised Danny in silence: he feared that Danny's phenomenal intelligence would lead him to lack compassion. Therefore he raised him in silence (as he was himself by his own father) so that he could find his own strength, yet he realized that Danny has indeed become a person with compassion. He also relates Danny to his older brother, who ran away from his homeland in Russia and became a professor, renounced his faith, and died in Auschwitz. He says that Reuven and his father came at just the right time in Danny's life when he was ready to rebel, and they helped Danny realize what he really wanted. Rabbi Saunders apologizes for his anger at Reuven and his father over Zionism. Rabbi Saunders says that it is okay if Danny doesn't become a rabbi. He has found his inner strength and will be a righteous man (Tzadik) to the entire world. Rabbi Saunders asks Danny if he will cut his beard and sideburns (payot). Danny responds he will. He then asks if he will still observe the commandments, which he says he will. Rabbi Saunders says that Passover is the holiday of freedom and that he must let Danny be free. He then leaves in tears saying that he is not wise. Danny then spends hours in tears and he and Reuven walk around the neighborhood in silence.
A few days later, Danny has cut his beard and sideburns and he says that he and his father now talk. On the last page, Danny and Reuven shake hands, knowing that they will always be best friends, and Danny then leaves to start his new life as a psychologist.