Paula tells Michael that she will not be bringing their daughter to Australia for Christmas. A deeply depressed Michael commits suicide in his hotel room. The band finds out about his death from watching the news.
Set in Australia in the late 1970's, the Perth-based band The Farriss Brothers are playing cover songs at pubs. The band consists of brothers Andrew, Jon, and Tim Farriss, and their friends Garry Gary Beers, Kirk Pengilly, and Michael Hutchence (Luke Arnold), the lead singer. After getting fired by their manager, they make the decision to never play covers again. They hire a new manager, who immediately changes their name to INXS (pronounced in excess), but later quits after the band refuses his suggestion to become a Christian band. They eventually hire their booking agent Chris Murphy (Damon Herriman) to be their new manager, but he will only take the job if they agree to be more than just another Australian band who can't find success outside of the continent.
At the outset of the 1980's, the band is becoming more successful in Australia. Chris is able to book a tour in the United States, but as the opening act for Adam Ant. They proceed to blow him off the stage musically, and soon they are the headline act. The band is on the road around the world for two years, but their long absence from home has led to Michael's girlfriend to break up with him. A newly single Michael soon begins a relationship with Kylie Minogue. As time goes by, Chris wants the band to be more successful in the US, and he tells them that their best songs are the ones written by Andrew and Michael, so he wants them to write all of the songs on their next album. That album, Kick, is initially rejected by their American record label, but Chris believes in it so much, he self-finances their US tour and begins the long process of getting the album on college radio. Both the tour and the radio play lead to Kick going quadruple platinum, their song "Need You Tonight" becomes their first number 1 song in the US, and the band starts winning numerous awards. By 1987, INXS is the hottest band in the world.
By the end of the Kick tour, the band is burned out and, despite Chris' objections, takes a year off. In that time, members of the band get married and work on side projects. Michael does a solo album, but it bombs because it's not INXS. He also dumps Kylie and starting dating supermodel Helena Christensen. A year later, the band releases their album X, and go back on tour. But with all of the success the band is getting overseas, the Australian press is beginning to criticize the band, claiming they have turned their backs on their homeland. The band responds by headlining a charity concert in Sydney, but it's deemed a failure and the backlash gets even worse. As a result, some members of the band choose to uproot their families and move out of the country.
As for Michael, he is still in Australia and still dating Helena. One night, a drunken Michael unknowingly insults a cab driver, and gets sucker punched. The result causes Michael to have headaches and to also lose his senses of smell and taste. He also begins to have bouts of rage, and eventually he takes out his rage on the rest of the band while recording their latest album on the Isle of Capri. After they finish the album, the band takes another break. A while later, Michael appears on a London talk show hosted by Paula Yates (Georgina Haig), the wife of British rock star Bob Geldof, and they begin an affair. Helena breaks up with Michael, and he and Paula, who announces she is divorcing Bob, move in together in London. They later have a child, Tiger Lily. Now a father, and with his rage issues under control, Michael makes up with the band and they record a new album and go on tour again. But he misses Paula and Tiger, and his recreational drug use is starting to get more hard core, and it's affecting his on stage performance.
It's now November of 1997, and the band is back home recording a new album and preparing for a homecoming tour of Australia. Following a recording session, Michael says goodbye to the band and returns to his hotel room. It's there he gets bad news from Paula. Because they are tired of being constantly chased by the British paparazzi, Michael and Paula want to move to Sydney. She is petitioning the court to allow her to take all of her kids to Australia to live with her and Michael because she doesn't want to separate Tiger from her half-sisters. Bob is contesting it in court, so Paula won't be bringing their daughter to Australia for Christmas. This sets Michael off into deep depression and he begins having suicidal thoughts. The next day, November 22, the band shows up at the studio, and once again laments that Michael is late. Tim, who had brought a TV to the studio to watch cricket, turns it on, only to see a news report that Michael was found dead in his hotel room. This is how INXS learned that Michael had hung himself. The rest of the band starts grieving, not only from the death of Michael, but the end of the band as they know it.
The movie ends with a flashback to when Andrew and Michael wrote their hit "Never Tear Us Apart", followed by concert footage of the real INXS performing the song.