In 1945, the New York City Corleone family don, Vito Corleone, listens to requests during his daughter Connie's wedding to Carlo. Vito's youngest son Michael, a Marine who has thus far stayed out of the family business, introduces his girlfriend, Kay Adams, to his family at the reception. Johnny Fontane, a popular singer and Vito's godson, seeks Vito's help in securing a movie role. Vito sends his consigliere, Tom Hagen, to persuade studio president Jack Woltz to offer Johnny the part. Woltz refuses Hagen's request at first, but soon complies after finding the severed head of his prized stud horse in his bed.

As Christmas approaches, drug baron Sollozzo asks Vito to invest in his narcotics business and for police protection. Vito declines, citing that involvement in narcotics would alienate his political connections. Suspicious of Sollozzo's partnership with the Tattaglia crime family, Vito sends his enforcer Luca Brasi to the Tattaglias on an espionage mission. Brasi is garroted to death during the initial meeting. Later, enforcers gun down Vito and coerce Hagen into a meeting. With Vito's first-born Sonny now in command, Sollozzo pressures Hagen to persuade Sonny to accept the narcotics deal. Vito survives the shooting and is visited in the hospital by Michael, who finds him unprotected after NYPD officers on Sollozzo's payroll cleared out Vito's guards. Michael thwarts the attempt on his father's life but is beaten by corrupt police captain Mark McCluskey. After the attempted hit at the hospital, Sonny retaliates with a hit on Bruno Tattaglia. Sollozzo and McCluskey request to meet with Michael and settle the dispute. Michael feigns interest and agrees to meet, but hatches a plan with Sonny and Corleone capo Clemenza to kill them and go into hiding. Michael meets Sollozzo and McCluskey at a Bronx restaurant; after retrieving a handgun planted in the bathroom by Clemenza, he shoots both men dead.

Despite a clampdown by the authorities for the killing of a police captain, the Five Families erupt in open warfare. Michael takes refuge in Sicily and Fredo, Vito's second son, is sheltered by Moe Greene in Las Vegas. Sonny publicly attacks and threatens Carlo for physically abusing Connie. When he abuses her again, Sonny speeds to their home but is ambushed and murdered by gangsters at a highway toll booth. In Sicily, Michael meets and marries a local woman, Apollonia, but she is killed shortly thereafter by a car bomb intended for him.

Devastated by Sonny's death and tired of war, Vito sets a meeting with the Five Families. He assures them that he will withdraw his opposition to their narcotics business and forgo avenging Sonny's murder. His safety guaranteed, Michael returns home to enter the family business and marry Kay. Kay gives birth to two children in the early 1950s. With his father nearing the end of his life and Fredo not suited to lead, Michael assumes the position of head of the Corleone family. Vito reveals to Michael that it was Don Barzini who ordered the hit on Sonny and warns him that Barzini would try to kill him at a meeting organized by a traitorous Corleone capo. With Vito's support, Michael relegates Hagen to managing operations in Las Vegas as he is not a "wartime consigliere". Michael travels to Las Vegas to buy out Greene's stake in the family's casinos and is dismayed to see that Fredo is more loyal to Greene than to his own family.

In 1955, Vito dies of a heart attack while playing with Michael's son Anthony. At Vito's funeral, Tessio asks Michael to meet with Barzini, signaling his betrayal. The meeting is set for the same day as the baptism of Connie's baby. While Michael stands at the altar as the child's godfather, Corleone hitmen murder the dons of the Five Families, plus Greene, and Tessio is executed for his treachery. Michael extracts Carlo's confession to playing a part in Sonny's murder. He assures Carlo that he is being exiled, not murdered, before Clemenza strangles Carlo. Connie confronts Michael about his involvement in Carlo's death while Kay is in the room. Kay asks Michael if she is telling the truth and is relieved when he denies carrying out the death. As she leaves, capos enter the office and pay reverence to Michael as "Don Corleone".