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Bruce Nolan (Jim Carrey) is a TV news reporter for the American Broadcasting Company affiliate television station (WKBW-TV) news team, Channel 7 Eyewitness News in Buffalo, New York who is unsuccessful at getting a job as an anchorman and, after a series of other bad luck incidents, complains to God that He is both treating him (Bruce) unfairly and is doing a poor job as supreme deity. Bruce is then contacted by God (Morgan Freeman), who grants Bruce all of His power so as to prove which one is the better handler thereof. Bruce quickly uses his new-found powers for personal gain: he sabotages a colleague named Evan, who cheated him; takes revenge on a street gang who badly beat him up earlier in the film; transforms his car from a Datsun 240Z to a Saleen S7; allows his favorite hockey team, the Buffalo Sabres, to move to the Stanley Cup; places command on a dog to use the toilet for defecation; and enhances his girlfriend's breasts and sex drive. He is then reminded that he has the task of resolving other people's problems. Meanwhile, Bruce endangers his relationship with his girlfriend Grace Connelly (Jennifer Aniston) through his self-centered behavior. Ultimately Bruce realizes that God's powers are best left for God to handle and graciously asks God to take control of his life.

The movie portrays God as a wise but a very elderly man. God quotes a line from one of Carrey's other movies ("Alrighty then", from Ace Ventura), and tells Bruce that if he wants, Bruce can fix all the world's problems in a few minutes, knowing full well from eons of experience that he cannot. Bruce later receives millions of prayers, all of which, according to God, originate only from a few streets in his own town. Bruce is thus able to realize just how much work God must do to keep creation "in line".

Bruce then begins to use his powers with more discretion: he examines prayers properly and does not grant all; apologizes to Evan and grants him the position in their work that both had desired; helps a homeless man who has appeared to him at times to convey philosophical speeches; assists a man whose car has broken down by helping him push it to work (after which the man says "God bless" to Bruce), and toilet-trains the aforementioned dog without using spiritual intervention. Moments later, Grace's sister Debbie cites a difference in the two siblings' routines, whereof the most significant comment is to the effect that Grace is often immersed in prayer. During that day's evening, as Bruce is receiving prayers he looks for one sent by Grace. Upon finding one, he uses his power to discover that she adores him, but wishes to cease the emotion on grounds that she perceives herself as a threat to him and wishes not to be so.

Depressed, Bruce walks onto a highway and is killed by collision with a truck. He is then shown in Heaven, where God asks him "what he really wants". In answer, Bruce asks that Grace find a man who may make her truly happy and see her through God's eyes. At this, God brings Bruce back to life. Later, Bruce has returned to his earlier field of reporting and is content with it; donates blood for a transfusion; and becomes engaged to marry Grace. The ending scene features a slow close-up picture of the homeless man, who is revealed to have been God in disguise. This echoes a line of Joan Osborne's song, One of Us, which Bruce is shown singing after his acquisition of the divine power.