Charlie Baileygates (Jim Carrey) is a veteran Rhode Island State Police trooper who has been taken advantage of by those around him, starting with his former wife Layla (Traylor Howard). Despite his friends warning him of Layla's infidelity, Charlie refused to accept she was in an affair, even after she gave birth to triplet black boys, until she ran off with her midget genius black lover, Shonté, abandoning her children. In the present, Charlie has raised the triplets as his own, Jamal, Lee Harvey, and Shonté Jr (Anthony Anderson, Jerod Mixon, Mongo Brownlee), likewise geniuses, but huge in size as compared to their biological father. While Charlie is consistently loved and respected by his "sons", he is continually abused by the rest of the town, who see him as a stupid coward whom anyone can easily walk over. As a result of years of such treatment, Charlie develops a split personality named Hank to deal with the confrontations Charlie avoids. Emerging whenever Charlie is under extreme stress, Hank is an over-the-top, rude, and violent persona reminiscent of characters played by Clint Eastwood. A psychiatrist prescribes medication to keep Charlie's Hank personality at bay.
Believing that Charlie needs a vacation, his commanding officer (Robert Forster) orders him to escort Irene Waters (Renée Zellweger) from Rhode Island to Massena, New York, because she reportedly committed a hit-and-run. Irene insists the hit-and-run accusation is a lie told by Dickie (Daniel Greene), her mob-connected ex-boyfriend, and by corrupt police officers in his employ, to keep her from revealing Dickie's illegal activities to the proper authorities. In Massena, Charlie prepares to turn over Irene to two United States Environmental Protection Agency (EPA) agents, when a hitman with a contract on Irene's life attempts to assassinate her, killing one of the EPA agents. Charlie keeps Irene safe, and they flee, accidentally leaving his medication behind, allowing the Hank personality to emerge frequently. Meanwhile, the FBI suspects that Charlie is responsible for the murder of the EPA agent. FBI agents begin pursuing him and Irene, as do crooked police officers in Dickie's pay, Boshane (Richard Jenkins) and Gerke (Chris Cooper). The chase becomes a media spectacle, alerting Charlie's sons to his predicament.
Charlie and Irene decide to return to Rhode Island, developing a bond along the way. Though Irene is taken by Charlie's personality, the frequent emergences by Hank worry her, though his more aggressive personality keeps them out of trouble. Along the way they pick up Casper aka "Whitey" (Michael Bowman), an albino waiter from a restaurant who claims he killed his entire family in the past. While stopping at a motel, Charlie discovers how he might be able to suppress Hank and goes to have a conversation with Irene about it, and they sleep together. The next morning, Hank reveals that actually it was he who slept with Irene. In the confusion, they are almost ambushed by Boshane and Gerke, but Charlie's sons, having found them, create a distraction, stealing a police helicopter, they call in a false report, stating Charlie and Irene have been spotted in the woods nearby, allowing Charlie and Irene to leave without knowing about the police who had left before they exited their room, leaving Casper behind.
They board a train back to Rhode Island. Dickie boards the same train, unable to rely on his henchmen to stop Charlie and Irene. He kidnaps her, and Charlie gives chase, working together with Hank to save her. Hank then appears to try to stop Charlie from rescuing her, but Charlie finally stands up for himself against his own fears, thus permanently nullifying Hank for good. As Charlie tries to wrestle her back and disarm Dickie on a bridge, Dickie shoots off his thumb. Dickie is then hit from behind by a lawn dart thrown by Casper, killing him. Charlie and Irene fall from the bridge into a river below, where Charlie's sons arrive to help rescue them. Regrouping with Casper, Charlie apologizes for making him kill again, but Casper reveals he made up his backstory due to the fact that Charlie talked too much at the motel and scared him. The police arrive but quickly learn of Irene's plight and the corrupt cops working for Dickie. Gerke is arrested, Charlie is congratulated for bringing him to justice, and Irene is cleared of the charges against her.
Irene prepares to leave Rhode Island when she is pulled over by the police, but this proves only to be a diversion to allow Charlie to propose marriage to her, which she happily accepts.
The post-credits scene sees everyone looking for Charlie's thumb in the river, Whitey finds it but a fish eats it.Jim Carrey as Charlie Baileygates/Hank EvansRenée Zellweger as Irene P. WatersChris Cooper as Lt. GerkeRobert Forster as Colonel PartingtonRichard Jenkins as Agent BoshaneZen Gesner as Agent PetersonMichael Bowman as Casper ("Whitey")Rob Moran as Trooper FinneranDaniel Greene as Dickie ThurmanAnthony Anderson as Jamal BaileygatesJeremy Maleek Leggett as 9-year-old Jamal BaileygatesMongo Brownlee as Lee Harvey BaileygatesAndrew Phillips as 9-year-old Lee Harvey BaileygatesJerod Mixon as Shonté Jr. BaileygatesJustin Chandler as 9-year-old Shonté Jr. BaileygatesTony Cox as ShontéSteve Tyler as Delivery Room DoctorTraylor Howard as Layla BaileygatesRichard Tyson as Gun shop ownerEzra Buzzington as Disabled guyShannon Whirry as Breastfeeding momLin Shaye (deleted scenes) as Mrs. CaleronLina Teal as Bikini girlAnna Kournikova, Cam Neely and Brendan Shanahan appear in cameo roles
The film's original score was written by Pete Yorn, while the movie's soundtrack contains several covers of Steely Dan songs performed by other bands. Examples are Smash Mouth's cover of "Do It Again", Ben Folds Five's cover of "Barrytown", and Marvelous 3's cover of "Reelin' in the Years". Other songs include "Breakout" by Foo Fighters, "Totalimmortal", originally by AFI but covered by The Offspring, "The World Ain't Slowin' Down" by Ellis Paul, and "Strange Condition" by Pete Yorn.
- "I'd Like That" – XTC
- "Breakout" – Foo Fighters
- "Do It Again"+ – Smash Mouth
- "Deep Inside of You" – Third Eye Blind
- "Totalimmortal" – The Offspring
- "The World Ain't Slowin' Down" – Ellis Paul
- "Any Major Dude Will Tell You"+ – Wilco
- "Only A Fool Would Say That"+ – Ivy
- "Can't Find The Time To Tell You" – Hootie & The Blowfish
- "Bodhisattva"+ – Brian Setzer Orchestra
- "Bad Sneakers"+ – The Push Stars
- "Reelin' In The Years"+ – Marvelous 3
- "Strange Condition" – Pete Yorn
- "Barrytown"+ – Ben Folds Five
- "Razor Boy"+ – Billy Goodrum
- "Where He Can Hide" – Tom Wolfe
+Steely Dan cover
"Motherfucker" by The Dwarves, "Fire Like This" by Hardknox, "Don't Say You Don't Remember" by Beverly Bremers, "The Perpetrator" by Hipster Daddy-O and the Handgrenades, and "Hem of Your Garment" by Cake were included in the movie but not on the soundtrack. Pete Yorn's, Just Another can also be heard it the background, during the scene where they discuss Hank's Idea. Alta Mira's "El Capitan" can be heard in the background, during the scene where Hank fights himself at the train station. Other songs, that appeared in the film are not included on the soundtrack album.
The film opened at #1 on the weekend of June 23, 2000 making US$24.2 million in its opening weekend. The film earned $90,570,999 in the United States, and a further $58,700,000 internationally for a worldwide total of $149,270,999.
Review website Rotten Tomatoes gave the film a score of 48%, based on 97 reviews, and an average rating of 5.4/10, with the consensus that "While Jim Carrey's comedic skills earn some laughs, Me, Myself and Irene sports a tired, unsatisfying plot."