The film's plot and narrative structure interweave the stories of several characters whose lives cross paths during events set against the backdrop of the turbulent middle/late 1960s. The story apparently takes place from about Late-1965 to Mid-1969.[1]

The story begins in Liverpool, England with a young shipyard worker named Jude (Jim Sturgess). Against the wishes of both his mother and his girlfriend, Jude enlists in the merchant navy and travels by a ship to the United States of America. He jumps ship in New York City to search for his American G.I. father, Wes Hubert (Robert Clohessy), whom he has never met and who does not know he exists. He learns that his father works at Princeton as a janitor. After meeting his father, Jude has nowhere to go. He befriends a Princeton student, Maxwell (Max) Carrigan (Joe Anderson), a rebellious and eccentric young man from a privileged background. Max and his friends come from upper class families who pay for their schooling, so they mess around, drink, and do drugs(With a Little Help From My Friends). When Max goes home for Thanksgiving, bringing Jude with him, Jude meets Max's younger sister Lucy (Evan Rachel Wood). After a heated argument with his parents about his future, Max drops out of college and moves to New York City, accompanied by Jude. Max works as a taxi driver, while Jude pursues work as a freelance artist. They become roommates in a bohemian enclave in Greenwich Village, where they share an apartment with others, most notably Sadie (Dana Fuchs), their landlady, who is an aspiring singer and a representation of Janis Joplin. Other residents include Jojo (Martin Luther McCoy) (who's name is a reference to the protagonist of the song Get Back) , a guitarist representing Jimi Hendrix, who arrives from Detroit, Michigan after the death of his younger brother during the 12th Street Riot(Let It Be)(Come Together); and Prudence (T. V. Carpio),(Named after the song, Dear Prudence) a young woman who has hitchhiked to New York City from Dayton, Ohio where she was seen pining after a fellow cheerleader. After Lucy's boyfriend, Daniel (Spencer Liff) is killed in Vietnam, she goes to New York City to visit Max before she starts college, despite the fact that her parents are against the idea (Why Don't We Do It In The Road).

Romantic relationships develop between Lucy and Jude (If I Fell), and between Sadie and Jojo (I Want You). One night, Prudence (who seemingly has a crush on Sadie) becomes depressed, and hides in a closet. Upon realizing where she is, the rest of the cast coax her out of the closet (Dear Prudence). Prudence mysteriously leaves the group after wandering off enthralled by street performers at a peace rally. As Sadie and Max discuss Prudence's now-empty room, Max uses a hammer to bang out the first 7 notes of Maxwell's Silver Hammer.

Sadie and her band, the Po Boys (reference to a line in "Down on the Corner"), with Jojo as her lead guitarist, are courted by a prospective manager, who invites them to a book function for an existential drug guru named Doctor Robert (Bono), based on Ken Kesey. After serving punch that appears to be laced with LSD (aka Kesey's Electric Kool-Aid), Doctor Robert lectures that the New Yorkers are two years behind the new agers of California, and urges everyone that "time is of the essence, we have to transcend fast"(I Am The Walrus).

The friends embark with Doctor Robert and his followers on an epic journey inside a psychedelically painted bus named "Beyond", an allusion to Ken Kesey's real-life bus "Furthur" They wake up not knowing where they are or how they got there, probably somewhere in Upstate New York. They learn Doctor Robert has taken them to the spiritual retreat compound of Dr. Frank Geary, a fellow psychonaut "Navigator", and leader of a cult called the "League of Spiritual Deliverance" (Geary is an allusion to Timothy Leary, who headed the International Foundation for Internal Freedom, from his estate in Millbrook). Mirroring the real-life refusal of Leary to commune with Kesey when the latter showed up unexpectedly at Leary's rural retreat house, Geary refuses to see Doctor Robert who, resigned to this news, retires to California. The friends, however, are stranded.

At the cult compound, the friends are reunited with Prudence, who now is a performer in the circus of "Mr Kite," (Eddie Izzard) a merry entertainer, who wants to challenge the world of show business with his "blue people" (a reference to the Blue Meanies from the Beatles 1968 movie Yellow Submarine). The Marry Pranksters can also be seen playing the instrumental part of the song "MR Kite"(Being for the Benefit of Mr. Kite)(Because).

When Max is drafted and sent to Vietnam, Lucy becomes involved in the anti-war movement, while Jude (who, despite potentially having U.S. citizenship due to his American father, is still living without a visa and thus can't be drafted) remains comparatively apolitical (Something). Jude becomes unhappy with the amount of time Lucy spends with a political group, "Students for a Democratic Republic" (SDR), an allusion to the real life group Students for a Democratic Society suspecting that its leader Paco is a lothario. Jude's art and his relationship with Lucy both start to falter(Strawberry Fields).

Meanwhile, Sadie has been signed to the prospective manager's record label, but he wants her to drop her backing band. She agrees, and this leads to a bitter break up between Sadie and Jojo, both musically and romantically. Sadie leaves to go on tour, while Jojo plays guitar in a local bar (Oh! Darling).

Meanwhile, the differences and tensions between Jude and Lucy escalate. One day, Jude storms into the SDR office where Lucy works and points out the activists' hypocrisy as well as the violence their actions invite, but he is thrown out by Paco's people (Revolution). This leads to an argument between the couple, which results in Lucy leaving Jude (While My Guitar Gently Weeps)(Across the Universe). Jude finds her at an anti-war demonstration at Columbia University during which many protesters, including Lucy, are arrested(Helter Skelter). Pushing through the crowd to help her, Jude is also beaten and arrested.

Lucy contacts Jude's father Wes, who convinces the police not to press charges, but he cannot prove that Jude is his son (and thus an American citizen), so Jude is deported to England. Going back to work at the Liverpool shipyards, Jude encounters his old girlfriend, Molly. She is now pregnant by Jude's old friend and shipyard co-worker Phil Scully, which does not upset the apathetic Jude.

Max is wounded in Vietnam and is repatriated, emotionally and mentally shattered by his experiences and dependent on morphine to relieve his pain, while Lucy remains involved in her anti-war movement, which is becoming more and more violent (much as the SDS broke apart, with hard-left extremists forming the domestic terrorist group The Weathermen). Lucy finally leaves the group when she returns to the SDR headquarters one night to find the offices deserted and Paco and some of his followers making bombs. One of their bombs explodes, killing Paco and his confederates and destroying the building, an allusion to the Greenwich Village townhouse explosion that killed three members of the Weather Underground in 1970 (Blackbird).

Jude reads about the explosion in a Liverpool newspaper and believes that Lucy has also been killed. However, he subsequently hears from Max that she is alive, and, encouraged both by a vision of Max singing "Hey Jude" to him and by his understanding mother, he arranges to legally return to the United States. He meets Max, who drives him to Sadie's music headquarters where a rooftop concert is underway that recalls the Beatles' famous 1969 performance. Jojo and Sadie have reunited, and their band (which now includes Prudence) sings "Don't Let Me Down". Lucy is supposed to be there, but she arrives late and cannot get into the building to join them on the roof. After seeing Sadie's recording company logo (an abstract strawberry Jude had created - a reference to the Beatles' Apple Corps), Lucy slowly walks away, overwhelmed with grief.

The police begin to force the group to leave, a specific reference to the Beatles' rooftop concert on January 30, 1969, where "Don't Let Me Down" was one of five songs sung by the Beatles before the concert was broken up by the police.[2] Jude manages to evade the police and stay behind on the roof. Hesitantly, he begins to sing "All You Need Is Love". Sadie, Jojo and the rest of the band hear him, and the police allow them to go back onto the roof to accompany him with their voices and instruments.

Down in the street, Lucy hears Jude as well and tries to enter the building, but is turned away by the police. Max suddenly looks out across the street as everybody else sings and, at the exact moment when John Lennon self-parodies in the original release, begins to sing "She Loves You" as Jude turns to see Lucy, who is wearing a diamond necklace and stands on an adjacent roof. Jude and Lucy smile at one another with tears in their eyes, and the screen fades out to white clouds and blue sky. This is a reference to "Lucy in the Sky with Diamonds," which commences in the background.