The New Orleans-born musician died on Thursday, per a message posted on his official Twitter account.
The Rock and Roll Hall of Fame singer combined the genres of blues, pop, jazz, jazz woogie, and rock and roll.
A statement said: “Towards the break of day June 6, iconic music legend Malcolm John Rebennack, Jr, referred to as Dr. John, kicked the bucket of an attack.”
The musician “created a novel mix of music that carried his hometown, New Orleans, at its heart because it was continuously in his heart,” it continues.
“The family thanks all who shared his distinctive musical journey & requests privacy at this point. Memorial arrangements are declared in due course.”
Blondie lead singer Debbie Harry was among those to pay tribute, sharing an image of herself alongside the six-time Grammy winner.
Former Beatles drummer Ringo Starr also tweeted an image, together with the message: “God bless Dr. John, peace and love to all his family. i really like the doctor, peace, and love.”
His career started in the late 1950s, once he became distinguished as a pianist and singer on the metropolis music scene.
Born Malcolm John Rebennack in New Orleans, his love of music was fostered by his father, who ran an appliance store that also sold-out records.
His mother, meanwhile, had worked as a model, and due to her connections, Malcolm’s face appeared on boxes of Ivory Soap.
Despite being kicked out of the church choir, he pursued his love of music, attending native clubs and working at a studio in town during his teens.
His first love was the guitar, however, he had to change to the piano after being shot while attempting to defend a bandmate who was being pistol-whipped in 1960.
“Ronnie was simply a child and his mother had told me ‘You better look out for my son,'” he told Smithsonian.com in 2009.
“Oh God, that was all I used to be pondering. I attempted to prevent the guy, I had my hand the barrel and he shot.”
He later became a part of the notable “Wrecking Crew” – a group of LA backing musicians who played on hits by Aretha Franklin, Van Morrison, Cher Frank Zappa, and countless others
The Dr. John character, modelled on a voodoo priest, was created in the late Sixties.
Rebennack at the start wished another singer to play the role, however after they force out at the last minute, “I simply did it myself out of spite,” he said.
“I never thought I’d be doing another record. I ne’er wished to be a frontman. All of a sudden, I got into it, and it wasn’t as bad as I believed.”
Blending New Orleans jazz, blues, and psychedelia, he gained recognition with the release of his album Gris-Gris in 1968; and scored a US top 10 hits in 1973 with Right Time, Wrong Place.
His live shows were known for their carnival atmosphere and he would wear costumes of bright colors, feathers, and plumes, and scatter glitter on the audience.
The musician, who with success battled drug addiction, was inducted into the Rock and Roll Hall of Fame by singer John Legend in 2011; and won his most recent Grammy in 2012 once bolted Down was named the best blues album. That album touched on drugs, his time in jail – he got a two-sentence for drug charges in the mid-60s – and efforts to repair his relationship along with his kids. He was married twice and told the New York Times he had “a lot” of kids.