NOTE: This spoiler was sent in by Pinch. who cals it..."A surprisingly good movie with a TON of cameos. It's not a movie that uses all the funny scenes in the trailer. It's a spot on parody of music biopics in the style of classics like Airplane.
The movie opens at a concert in the present day. A backstage crew member tells Dewey Cox that it's showtime. Sam the drummer (Tim Meadows) tells the crew guy that Dewey has to reflect on his entire life before he performs.
We flashback to Dewey as a young child watching his brother Nate play the piano. Nate is a phenomenal pianist. The two boys go out and play in a montage of dangerous activities like being chased by a bull, speeding on a tractor, etc. Eventually they end up in a barn and decide to have a machete fight. Dewey ends up "halving" his brother. Nate tells Dewey he has to be twice as great now for the both of them. The doctor comes, but is unable to save Nate. Dewey's angry father tells him it should've been Dewey who died. Dewey loses his sense of smell. His mother sends him to the store for an errand and he meets a couple of bluesmen. They teach him to play the guitar and he sings a song about cutting his brother in half.
Moving forward in time a high school Dewey (now played by John C Reilly) plays at a talent show where his music causes everyone to get up and dance and fight. It's proclaimed to be the devil's music, so Dewey leaves town with his teenage sweet heart, Edith, played by the 30 something Kristen Wiig. She tells him she'll always believe in him, but continually follows that up with, "but I know you're gonna fail" even during all the levels of success he'll achieve later.
Dewey is mopping floors at a black club mimicking the moves of the leader of the house band, but not getting any respect. Dewey's time to shine comes when the band leader can't perform because he broke both his hands and lost his voice. This is where Dewey first meets Sam the drummer. Dewey fills in when three Jewish talent scouts are in the audience. They love Dewey and sign him to make a record.
Dewey unsuccessfully tries to please the sound engineer by playing the songs the record label wanted him to play, but ultimately wins him over by playing an original song he wrote "Walk Hard". The back up band (Meadows along with SNL's Chris Parnell and UCB's Matt Besser) comically "follows Dewey's lead" and the song is a hit on the first take.
Dewey starts getting booked with big stars like Buddy Holly and Elvis (played brilliantly by Jack White from the White Stripes). Sam introduces Dewey to weed. Eventually this leads to Dewey taking up with groupies and cheating on Edith, who is now his wife.
Dewey's dad comes to tell him that his mother died while dancing to his music on the radio. She tripped on the cord, fell out the window and the radio crushed her skull.
Dewey continues to gain success and Sam continues to introduce him to harder drugs. A cocaine bust sends Dewey to prison, but his agent (Harold Ramis) tells him the best way out is to go to rehab. Dewey enters rehab and a treatment of adding and removing blankets eventually cleans him up....which doesn't translate nearly as funny as a spoiler as much as it does in the film.
Clean Dewey hires Darlene Madison (Jenna Fischer) to sing a duet loaded with double entendres with him. The sexual tension between the two of them becomes too much and they end up getting married...which doesn't do well with Edith, who is also currently still married to him as well. Edith leaves him and takes Dewey's many, many kids with her.
In the 60s Dewey becomes an activist for a variety of silly causes. He goes to India to meditate with the Maharishi and meets up with the Beatles who introduce Dewey to acid. Dewey has a bad trip because of the guilt he has from cutting his brother in half. Dewey now enters his experimental drug fused music period that has so many back up musicians that his original three piece back up band leaves.
Darlene is upset that Dewey is so back into drugs that she asks him to clean himself up again. He promises he will, but immediately eats some PCP while they hug. He then strips down to a loin cloth and runs wild in the street throwing cars around and scaling a building. Darlene leaves him.
In rehab again, the ghost of Dewey's brother visits him and tells him to stop acting like an idiot because he was supposed to be twice as great for the both of them. He tells Dewey to write his masterpiece. The ghost of Nate tells Dewey to talk to their dad for inspiration.
After rehab Dewey visits his father and apologizes His father forgives him and tells him that cutting him in half will square everything up. The two have a machete fight, but Pa Cox accidentally halves himself with his own machete. He tells Dewey to be a better father than he was....which shouldn't be too hard since he spent Dewey's entire life telling him that he should've died instead of his brother.
Dewey meets all of his kids and builds a relationship with all of them in a montage...thank God for montages! Instead of cutting to the chase for this film, after all of this should just be the Walk Hard montage. Anyway...Darlene comes back and is happy that Dewey finally realized the importance of family. His sense of smell comes back when he smells Darlene's hair.
The son of Dewey's agent visits and shows Dewey how a rapper named Lil' Nutzzak made a video sampling the song Walk Hard and suggests that Dewey tour with him explaining that Cox and Nutzzak make a nice package. He also tells him that because of this new interest in his career, Dewey will be awarded a Lifetime Achievement Award. Dewey makes ammends with his old band and they get back together to perform at the award show.
At the show, Jackson Browne, Lyle Lovett, Jewel and Ghostface Killah cover the song Walk Hard. Backstage Dewey fights his temptations. Sam tries to introduce Dewey to Viagra, the grand daughters of girls that Dewey banged in the past come on to him and literally the Temptations are rehearsing. Dewey finds alone time to reflect on his entire life....from the first scene of the movie.
On stage Eddie Vedder pokes fun at himself in an overly dramatic introduction of Dewey comparing musical pioneers to people from the bible. Dewey Cox takes the stage one last time and sings his masterpiece "Beautiful Ride". He dies three minutes after performing.
Young Dewey Cox accidentally cuts his brother in half with a machete and runs away from home pursuing his dream of being a great musician for both himself and his brother. Along the way he gets married, does drugs, reinvents himself and ultimately realizes the importance of family.
The resurgence of rap songs sampling classics leads to Dewey getting a Life time Achievement Award. He performs his masterpiece at the award show and dies immediately after.