A family friend called 911 around midnight Thursday after he went to check on Cornell and found the musician "unresponsive" on the bathroom floor at the MGM Grand hotel, spokesman Michael Woody said. Emergency medical personnel arrived, and Cornell was pronounced dead at the scene, he said.
"We are moving in the direction of a possible suicide but we are waiting on the Medical Examiner's Office to provide their report," Woody said.
Cornell was in Detroit performing with Soundgarden on a US tour that kicked off last month. His passing was "sudden and unexpected," his representative, Brian Bumbery, said in a statement to CNN.
"His wife Vicky and family were shocked to learn of his sudden and unexpected passing, and they will be working closely with the medical examiner to determine the cause," the statement read. "They would like to thank his fans for their continuous love and loyalty and ask that their privacy be respected at this time."
The Grammy-winning rocker had performed Wednesday night at the Fox Theatre in Detroit. He ended his performance with a cover of Led Zeppelin's "In My Time of Dying."
"Full set with an encore. Nothing odd. Outstanding performance," Bill Lowe of Port Clinton, Ohio, said, describing the show in a text message to CNN.
The grunge era
Cornell began his career in the Seattle rock scene. In 1984, he formed the band Soundgarden, which was influential in the 1990s grunge movement.
In death, Cornell becomes another in a line of lead singers from major grunge rock bands to pass away. Nirvana's Kurt Cobain was found dead in his Seattle home in 1994; his death was ruled a suicide. Alice in Chains' original singer, Layne Staley, died from a drug overdose in 2002. Scott Weiland of Stone Temple Pilots died of an accidental overdose in 2015.
In interviews, Cornell discussed his past struggles with alcohol and the impact of his friends' deaths from substance abuse.
"I've lost a lot of young, brilliant friends, people that I thought were very inspired," he told Rolling Stone in 2015. "They're all young and these guys all had limitless potential in their lives in front of them."
Soundgarden and Audioslave
Soundgarden predated both grunge pioneers Nirvana and Pearl Jam, but it wasn't an overnight success.
The group hit its commercial peak with its breakout album, "Superunknown," in 1994, which was nominated for a Grammy Award for best rock album. Songs from that album, "Black Hole Sun," won the Grammy that year for best hard rock performance, and the song "Spoonman" won for best metal performance.
The group disbanded in 1997 and released a greatest hits compilation the same year.
The breakup wasn't anything unusual, Cornell told CNN in 2012. "It was just time for a break," he said.
In 2001, Cornell joined with three former members of Rage Against the Machine to form Audioslave. Their most successful single, "Like a Stone," released in 2003.
The group's defining moment was a 2005 concert in Cuba, which at the time was billed as the country's first outdoor rock concert by an American band.
As the charismatic frontman, Cornell was known for his raw and soulful voice.
He also sang the theme song to the James Bond movie "Casino Royale" and released five solo albums
Remembering the rock star
Soundgarden came back on stage in 2010 for festival performances and had recently started touring again. The band tweeted Wednesday night a quote from Cornell: "What I look forward to the most...is the camaraderie. It's what we missed when we weren't a band."
Rocker Dave Navarro mourned the loss of Cornell, tweeting: "Such a terrible and sad loss! Thinking of his family tonight! RIP."
Cornell said he offered minimal explanation for his songs because he wanted fans to come up with their own meanings.
"If I write a song and put it out there, it's not mine anymore," he told CNN. "It takes on a life of its own, and when you listen to it, it becomes your song. And over the course of generations, those meanings will change."