According to a message on Thursday, posted on his official Twitter account, said that the New Orleans-born musician was dead.
The Rock and Roll Hall of Fame singer combined the genres of blues, pop, jazz, boogie woogie and rock and roll.
A statement said: “Towards the break of day June 6, iconic music legend Malcolm John Rebennack, Jr, known as Dr John, passed away of a heart attack.”
The musician “created a unique blend of music which carried his hometown, New Orleans, at its heart, as it was always in his heart,” it continued.
“The family thanks all whom shared his unique musical journey & requests privacy at this time. Memorial arrangements will be announced in due course.”
Former Beatles drummer Ringo Starr also tweeted a picture, along with the message: “God bless Dr John, peace and love to all his family. I love the doctor, peace and love.”
His career started in the late 1950s, when he became prominent as a pianist and singer on the New Orleans 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 records.
His mother, meanwhile, had worked as a model, and thanks to her connections, Malcolm’s face appeared on boxes of Ivory Soap.
His live shows were known for their carnival atmosphere and he would wear costumes of bright colours, feathers and plumes, and scatter glitter on the audience.
The musician, who successfully battled heroin 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 when Locked Down was named best blues album.
That album touched on drugs, his time in prison – he got a two-year sentence for drug charges in the mid-60s – and efforts to repair his relationship with his children.
He was married twice and told the New York Times he had “a lot” of children.
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