The film opens in 1968 at St. Anne's Academy, a California Roman Catholic school, where a young girl named Deloris Wilson is scolded by Sister Immaculata (Lois de Banzie) for wisecracking and disobedience. The setting then changes to the present day, where Deloris (now going by the surname Van Cartier) is a lounge singer in a 1960s-themed act called The Ronelles (a parody of The Ronettes), who sing at The Moonlite Lounge of the Nevada Club in Reno, Nevada, run by her boyfriend, the mobster Vince LaRocca. After Deloris walks in on Vince having his chauffeur Ernie executed for betrayal, Vince orders his two henchmen Joey and Willy to kill her as well. Deloris flees Vince's casino to the local police station where Lieutenant Eddie Souther suggests she testify against Vince if he can be arrested and tried, but for now, she should go into witness protection until the time comes.
Deloris is taken to St. Katherine's Parish in a seedy, run-down neighborhood of San Francisco, where Souther suggests she take refuge in the attached convent. Both Deloris and the stoic Reverend Mother object, but are convinced by Souther and Monsignor O'Hara to go ahead with it. Deloris 'becomes' a nun   habit and all   under the hand of Reverend Mother, who gives her the religious name 'Sister Mary Clarence' to complete the disguise. Mary Clarence objects to following the strictures and simple life of the convent, but comes to befriend several of the nuns, including the forever jolly Sister Mary Patrick, quiet and meek Sister Mary Robert, and the elderly deadpan Sister Mary Lazarus. After sneaking into a nearby bar, Mary Clarence is chastised by Reverend Mother and put into the choir, which she has seen to be dreadful. The choir nuns, learning that Mary Clarence has a background in music, elect her to take over as choir director, which she accepts, and she rearranges them to make them better singers. At Mass one Sunday, the choir sings the "Hail Holy Queen" in the traditional manner beautifully before shifting into a gospel and rock-and-roll-infused performance of the hymn.
Reverend Mother is infuriated with Mary Clarence about the performance, and orders that Mary Lazarus once again become the leader the choir, but Monsignor O'Hara is thrilled with the performance as the unorthodox music brought people, including teenagers, in off the streets. Deloris convinces Monsignor O'Hara that the nuns should be going out to clean up the neighborhood. This they do, and the choir wows church visitors with their music, with Souther eventually attending a performance of "My Guy" (appropriately rewritten as "My God"). Eventually, O'Hara announces to the choir that Pope John Paul II is to visit the church to see the choir himself. Reverend Mother decides to hand in her resignation since her authority has been unintentionally undermined, but Mary Clarence offers to leave in her stead, to which the Reverend Mother disagrees.
Detective Tate, a police officer on Vince's payroll, finds out where Deloris is and contacts Vince, who sends Joey and Willy out to grab her. Souther confronts Tate, gets him arrested, and flies to San Francisco to try and warn Mary Clarence, but Vince's men abduct her.
The nuns, led by the Reverend Mother, risk their lives by going to Reno to save Mary Clarence. Meanwhile, she flees Vince and his men, leading to a chase around the casino until the nuns find her and try to sneak out. Vince, Joey and Willy confront the nuns, but they are unable to bring themselves to shoot Deloris while she is in a nun's habit, and Reverend Mother proclaims Deloris is indeed a nun, to convince Vince. As Vince works up the courage to shoot her anyway, Souther bursts in and shoots him in the arm, and has the men arrested. Reverend Mother then thanks Deloris for everything she has done for them and agrees to remain at the convent.
The film ends with the choir, led by Deloris, singing "I Will Follow Him" before the Pope and a packed and refurbished St. Katherine's, earning a loud standing ovation from the audience, the Pope, Reverend Mother, Monsignor O'Hara and Lt. Souther. The end credits reveals that Deloris' secret life as a nun was sold to the media and has become a sensation. The ending of Deloris' "career" as a choir leader is revealed through magazines and album covers and Deloris has continued leading the choir as a famous group with published albums.
Output: What Catholic leader is to come to the convent?