A parody of the biopic genre, Walk Hard is the story of a fictional early rock and roll star played by Reilly.

Walk Hard primarily references the musical biopics Ray (2004) and Walk the Line (2005); in addition to Ray Charles and Johnny Cash, the "Dewey Cox" character includes elements of the lives and careers of other notable musicians including Roy Orbison, Glen Campbell, Bob Dylan, Jerry Lee Lewis, Donovan, John Lennon, James Brown, Jim Morrison, Conway Twitty, Neil Diamond, Hank Williams, and Brian Wilson.

In addition, the film parodies or pays tribute to the musical styles of David Bowie, Billy Joel, Van Dyke Parks, the Gun Club, and seventies punk rock.

In 1953, Dewey performs at a school talent show and drives the crowd wild with his song "Take My Hand," and his father kicks him out of the house, calling it the "Devil's music".

Working at an all-African American nightclub, Dewey replaces singer Bobby Shad onstage and impresses Hasidic Jew record executive L'Chaim.

A desperate Dewey performs "Walk Hard," a song inspired by a speech he gave Edith, which restores the executive's belief in Judaism and rockets him to superstardom.

Choir-girl Darlene Madison enters Dewey's life, and he produces several sexually suggestive hit records amid their courtship.

In the next scene, a music video shows that Dewey's new song mimics Dylan's style, including opaque lyrics ("The mouse with the overbite explained/how the rabbits were ensnared/ and the skinny scanty sylph/ trashed the apothecary diplomat/ inside the three-eyed monkey/ within inches of his toaster-oven life.").

The band resents his insane musical style and abusive behavior and breaks up; Darlene, also unable to deal with him, leaves him for Glen Campbell.

In 2007, L'Chaim's son Dreidel informs Dewey of his popularity with young listeners through rapper Lil' Nutzzak's sampling of "Walk Hard."

A title card reveals that Dewey died three minutes after this final performance, which then also reads "Dewford Randolph Cox, 1936–2007."

Apatow and Kasdan noted that they watched various types of biopics for inspiration, including those of Jimi Hendrix and Marilyn Monroe.

The site's consensus states: "A parody that pokes fun at rock stars and reductive biopics alike, this comedy sings in large part because of stellar performances and clever original music.

"[14] Peter Travers of Rolling Stone magazine wrote: "The tricky thing about parody movies is that the jokes get old fast and they're hit-and-miss.

[19] Along with a backing band "The Hardwalkers", Reilly made seven musical appearances as Dewey Cox in the weeks prior to the film's release date.