The King of Pop was pronounced dead after being rushed to UCLA hospital in Los Angeles in a deep coma, city and law enforcement sources told The LA Times.
Paramedics called to his home in LA found him not breathing. He was given CPR as the ambulance raced to hospital, a fire department captain told the LA Times newspaper.
Joe Jackson, the star's father, told showbiz website TMZ.com before the confirmation of his son's death: "He is not doing well."
Jackson had been about to embark on a comeback, performing 50 concerts at London's O2 Arena.
The concerts had been due to start on July 13 and Jackson had been rehearsing in the LA for the London shows, which sold out within hours of going on sale in March.
Sky's entertainment correspondent, Steve Hargrave said: "We can't underestimate the effect this will have on Michael Jackson fans who have loved his music and career.
"They would have been assuming that in about three weeks time their idol would have been back on the stage perfoming his greatest hits. To suddenly find out this news will be devastating.
Matt Blank from the Michael Jackson World Network fanclub told BBC News 24 he was "a bit dumfounded and a bit shellshocked by it all".
He said: "I find it hard to believe this could be a reality.
"In the past, health issues of Michael Jackson have always been rumoured. I can only imagine this is down to the amount of stress he was under to come out and perform."
He added: "It's just unimaginable that Michael Jackson is no more, it's just unbelievable."
Fans are arriving outside the hospital.