Hampton, known as the "granddaddy of the jam scene," collapsed on stage while rocking out Monday night during a concert held in his honor in Atlanta.
His agent, Micah Davidson of Midwood Entertainment, confirmed to CNN that the musician died. He gave no further details.
Warren Haynes, the Allman Brothers Band guitarist who was on stage performing with Hampton, posted a statement Tuesday on his official Facebook page asking for privacy for Hampton's loved ones.
"After collapsing on stage surrounded by his friends, family, fans and the people he loved, Col. Bruce Hampton has passed away," the statement said. "The family is asking for respect and privacy at this difficult time."
The all-star event, held at Atlanta's Fox Theatre, was billed as "Hampton 70: A Celebration of Col. Bruce Hampton."
The stage was packed with performers -- including Dave Schools of Widespread Panic, Phish drummer Jon Fishman and Rolling Stones keyboardist Chuck Leavell -- when the seasoned musician appeared to take a knee, then lay down as 14-year-old guitarist Brandon "Taz" Niederauer shredded chords on one of Hampton's favorite songs, "Turn on Your Love Light."
Some in the audience thought the guitarist's actions were a part of the show.
Those on stage continued to perform. They included Blues Traveler frontman John Popper, R.E.M. guitarist Peter Buck and Susan Tedeschi and Derek Trucks of the Tedeschi Trucks Band.
Then people came out from the wings and carried Hampton off stage. The song abruptly ended.
An ambulance arrived shortly thereafter and took Hampton away as dozens of bewildered fans watched quietly.
Born and raised Gustav Valentine Berglund III in New York City, Hampton was beloved in the music industry as a founding member of the rock blues quintet the Hampton Grease Band, which got its start in Atlanta.
While the band released only one album, "Music to Eat" in 1971, it developed a bit of a cult following, and Hampton went on earn a reputation as one of the best jam musicians in the industry.
He was the subject of a 2012 documentary, "Basically Frightened: The Musical Madness of Colonel Bruce Hampton."
Hampton he gave an interview in 2015 to the site Live For Live Music
in preparation for his reunion tour with the Aquarium Rescue Unit.
He spoke of his extensive career, which stretched from playing in bands in the 1970s to doing voice-over work in commercials for brands such as Popeyes fried chicken and Motel 6.
"I was a lasso instructor and a lariat importer, and they were all weird, fleeting jobs," he told the site. "I've been fortunate to do music all my life, and I've done enough acting to make it fun."
Fans, including a few famous ones, grieved Hampton on Tuesday.
"So so sad to say goodbye to the great & wondrous Col. Bruce Hampton," Chris Robinson of The Black Crowes and Chris Robinson Brotherhood told CNN in a statement. "The music world lost one of a kind last night, a true original, a man who heard the light! God speed Col. Bruce, we miss you."
Added longtime friend Oliver Wood of The Wood Brothers, "Just by example, he taught us to challenge our ideas about music and what it's for. Bruce was equal parts prankster and mystic. He was serious about music, but also taught us not to take ourselves too seriously. He was a one of a kind human. What an honor to be with him on his final night."
Vocalist and saxophonist Karl Denson called Hampton "the poet of some undefined movement that all the artists came to for wisdom and clarity."
"Once you connected with him, you felt inspired not to be jive, to know what was important and take chances," Denson said in a statement. "Most of all, he made us supremely happy."
Leavell, the keyboardist who tours with The Rolling Stones and was part of the Allman Brothers Band in the 1970s, said Hampton died doing what he loved.
"A poetic exit," Leavell said. "And I'm sure if he had written the script himself, that would've been the last page of the last chapter."
Previous versions of this story reported that Billy Bob Thornton was in attendance at Monday night's performance. While he was scheduled to perform, CNN has learned he was not there.