Raised on a sharecropping plantation in Northern Florida, Ray Charles Robinson went blind at the age of seven, shortly after witnessing his younger brother drown. Inspired by a fiercely independent mother who insisted he make his own way in the world, Charles found his calling and his gift behind a piano keyboard. Touring across the chitlin circuit, the soulful singer gained a reputation before exploding onto the worldwide stage when he pioneered the incorporation of rhythm and blues, rock and roll, gospel, country, jazz and orchestral influences into his inimitable style.
"Joliet" Jake Blues (John Belushi) is released from prison after serving three years for armed robbery. Jake is irritated at being picked up by his brother Elwood (Dan Aykroyd) in the Bluesmobile, a battered former Mount Prospect police car, instead of the Cadillac the brothers used to own. The brothers visit their childhood home, a Roman Catholic orphanage, and learn that it will be closed unless $5,000 in property taxes is collected. The brothers visit an evangelical church service where Jake has an epiphany: they can legitimately raise the funds by re-forming their rhythm and blues band. Elwood calls the quest "a mission from God.
18 years after the events in the previous film, Elwood Blues (Dan Aykroyd) is being released from prison, this time a modern private prison rather than the old Joliet Prison Illinois state penitentiary of his brother Joliet Jake's previous incarceration. He is told for the first time that his brother "Joliet" Jake Blues (John Belushi) has died, as has their surrogate father figure Curtis (Cab Calloway), then finds out that the orphanage the Blues Brothers had saved has been demolished.
The film centers on two main characters: Lazarus Redd (Samuel L. Jackson), a deeply religious farmer and former blues guitarist, and Rae Doole (Christina Ricci), a young sex addict. Lazarus' wife and his brother were having an affair, which has left him bitter and angry. Rae's boyfriend Ronnie Morgan (Justin Timberlake) leaves for deployment with the 196th Field Artillery Brigade, Tennessee National Guard, and in his absence, she indulges in bouts of promiscuity and drug use. During one of Rae's binges, Ronnie's friend Gill Morton (Michael Raymond-James) tries to take advantage of her. She laughs at his advances, comparing him unfavorably with another man, and he severely beats her. Believing she's dead, Gill dumps Rae and leaves her for dead in only a shirt and panties by the side of the road and drives away.
Leonard Chess, a Polish immigrant of Jewish descent, starts the record label Chess Records in Chicago in 1950. It opens its doors for black musicians and attracts people such as Muddy Waters, Chuck Berry, Little Walter and Etta James.
Eugene Martone (Ralph Macchio) is a classical guitar student at the Juilliard School for Performing Arts in New York City who has an obsession for the blues, especially the famed Robert Johnson. Most intriguing are the legends surrounding exactly how Johnson became so talented most notably the one claiming he "sold his soul to the Devil at the crossroads" along with a supposed lost song that Johnson never recorded.
On his way to see Wild Man Moore (Louis Armstrong) at the train station, Ram Bowen (Paul Newman), a jazz musician, encounters Connie Lampson, (Diahann Carroll), a newly arrived tourist, and invites her to see him perform that night at Club 33. Connie isn't interested but her friend, Lillian (Joanne Woodward) insists they go to see him. After Ram finishes performing with his friend Eddie (Sidney Poitier) offers to take both women to breakfast. When Ram suggests that he and Connie go off and have a private breakfast together she is offended and Ram is angered at being rejected. However Lillian, undeterred that Ram prefers her friend, pursues him and the two sleep together while Connie and Eddie spend the night walking around Paris.
Will Handy grandit à Memphis avec son père (pasteur) et sa tante Hagar. Son père entend, bien qu'il utilise ses dons musicaux uniquement à des fins religieuses à l'église, mais Will n'arrive pas à se séparer de la musique de rue de son époque. Après avoir écrit une première chanson, Gogo, une chanteuse, arrive à le convaincre de l'accompagner. Will est étranglé par la culture forte de son père et ses chansons de blues. Enfin la famille se réunit quand Gogo les fait venir à New York pour voir Will chanter une de ses chansons au milieu d'un orchestre symphonique.
À travers des interviews, des documents historiques, des reconstitutions par des acteurs et des interprétations de leurs chansons par des artistes actuels, Wim Wenders met en lumière ses artistes de blues préférés : Skip James, Blind Willie Johnson et J.B. Lenoir
Clint Eastwood, amoureux du jazz et du blues, et pianiste lui-même, se propose de retracer l'histoire du piano dans le blues à travers ceux qui l'ont popularisé au XX siècle. Il choisit de rencontrer Dr. John, Fats Domino, Little Richard, Jay McShann, Dave Brubeck, Pinetop Perkins, Marcia Ball et bien sûr Ray Charles. De nombreuses séquences d'archives ponctuent le film avec de grands noms du piano comme Otis Spann, Charles Brown, etc.
En suivant le voyage de Corey Harris au Mississippi et en Afrique de l'ouest, il présente les origines du blues dans le delta du grand fleuve américain, et sa parenté avec les musiques traditionnelles du Mali et du Niger.