The Los Angeles coroner, Fred Corral, said that Jackson was pronounced dead after arriving at UCLA Medical Centre in full cardiac arrest. A post mortem examination is likely to take place today.
Paramedics who responded to an emergency call to the singer's home in Los Angeles said that he had stopped breathing by the time they arrived.
Jackson's brother Jermaine told reporters: "My brother, the legendary King of Pop , passed away on Thursday June 25 at 2.26pm.
"We believe he suffered a cardiac arrest at his home, however the cause of his death is unknown until the results of the autopsy are known. The personal physician who was with him at the time attempted to resuscitated him."
A spokesman for the medical centre added: "When he arrived at hospital at approximately 1.14pm a team of doctors including emergency physicians and cardiologists attempted to resuscitate him for a period of more than one hour, they were unsuccessful."
A Los Angeles police spokesman said that police robbery-homicide detectives have been ordered to investigate, which is common in high-profile cases.
Jackson's mother Katherine and sister La Toya had rushed to the singer's bedside at the hospital, while hundreds of tearful fans gathered outside.
Earlier, the singer's father Joe said that he had been told his son was "in a bad way".
Jackson is widely credited with revolutionising pop music with albums including Thriller, Bad and Dangerous but his career was tainted with allegations of child abuse.
He was due to perform a highly anticipated 50-date "farewell" residency at the O2 Arena in Greenwich, south-east London, starting next month. Fears for his health emerged after he postponed the earliest dates, and his aides were forced to deny that he was fighting skin cancer.
Jackson lived as a virtual recluse following his 2005 acquittal on charges including child molestation and kidnap.
While lauded by fans and critics for his infectious pop songs, pioneering dance moves and innovative videos, his increasingly eccentric behaviour earned him the nickname "Wacko Jacko".
He repeatedly denied undergoing cosmetic surgery, despite very visible changes to his face and skin tone, and was criticised for forcing his three children to wear veils whenever they were in public.
Last night leading figures in the entertainment industry expressed their shock at news of his sudden death, which was broken on the US celebrity website TMZ.
Quincy Jones, the music producer who worked with Jackson on Thriller, said: "I am absolutely devastated at this tragic and unexpected news."
Paying tribute to the singer's "talent, grace, professionalism and dedication", he added: "I've lost my little brother today, and part of my soul has gone with him."
Jackson's friend, the illusionist Uri Geller, said there had been no indication that the singer was in a frail condition. "I really have no words. He was a young and terribly fit man and he was getting ready for performances in England. He was just fine, the last I heard."
There was speculation that the pressure of his upcoming London dates may have been too much for him. Jackson last toured 12 years ago.
AEG Live, which organised the O2 concerts, said Jackson had passed a lengthy physical exam in early 2009.
But Max Clifford, the publicist and friend of Jackson, said: "You wonder if the strain of getting fit for this major tour proved too much. In recent pictures he looked anything but healthy. He was always someone who seemed to find it difficult to cope with fame."
Born in 1958, Jackson made his musical debut with four of his older brothers in the Jackson Five before embarking on a solo career.
His 1982 album Thriller - which included the hits Beat It, Billie Jean and Thriller - is still the best-selling album of all time, with more than 26?million copies sold. His lifetime sales tally is estimated at 750?million.
In 1994, he married Lisa Marie Presley, the 26-year-old daughter of Elvis Presley. The couple separated two years later and Jackson later married Debbie Rowe, a 37-year-old nurse he met while undergoing plastic surgery in 1997. They had two children, Prince Michael and Paris Michael Katherine, before divorcing in 1999.
Jackson had custody of the two children and of a third, Prince Michael II, whose mother's name has never been made public.