Life for many in tiny Springberry, Alabama during the 1940s is fraught with hardship, misery, and poverty. The hand-to-mouth existence on a dingy farm outside of Springberry is even tougher, especially for a little boy named Dewey Cox (Conner Rayburn). The second of two Cox brothers, Dewey is cast in the shadow of his talented older brother, Nate (Chip Hormess), who is the apple of Pa Cox’s (Raymond J. Barry) eye. During an ill-fated childhood game that features a razor-sharp machete, Nate is cut in half and Dewey is thrown into a deep funk that claims not only his innocence but also his sense of smell. Only his love for the blues and playing guitar rescues him from a life riddled with guilt and depression.

At age 14, a performance at a local talent show becomes a seminal moment as the crowd reacts to his innocuous song, “Take My Hand,” with wild abandon. Because of this, Dewey (now played by John C. Reilly) is forced to leave town with his new girlfriend, Edith (Kristen Wiig), to escape the scornful eye of Pa Cox and the harsh life of Springberry. Heading out into the world to pursue the promise of his music, Dewey and Edith soon marry and have a gaggle of children while Dewey’s dreams of musical glory languish amid the diapers and unpaid bills as he continues to write songs that may never be heard.

While sweeping floors as the only white man in an African-American jazz club, Dewey gets his chance to perform when the headliner is unable to play one evening. Watching his triumphant performance of the blues standard “Mama, You Got to Love Your Negro Man” are record executives L’Chai’m (Harold Ramis), Mazeltov (Phil Rosenthal), and Schmendrick (Martin Starr), who arrange for Dewey to record a song at the famous Planet Records studio. There, Dewey performs “Walk Hard,” the song that would become his signature hit. He gains not only a recording contract but his first and only backing band: drummer Sam (Tim Meadows), whom he first met at the jazz club; guitarist Dave (Matt Besser); and bass player Theo (Chris Parnell)…..