Much of Cash’s music personified his character: a haunted, dignified, resilient spokesman for the working man.
"Johnny died due to complications from diabetes, which resulted in respiratory failure," Cash's manager, Lou Robin, said in a statement.
He said Cash died at the hospital at 5am GMT.
"I hope that friends and fans of Johnny will pray for the Cash family to find comfort during this very difficult time," Robin said.
Cash had been released from the hospital on Wednesday after a two-week stay for treatment of an unspecified stomach ailment. The illness caused him to miss last month's MTV Music awards, where he had been nominated in seven categories.
Cash had battled a disease of the nervous system, autonomic neuropathy, and pneumonia in recent years.
Clothing symbolised persona
In his 1971 hit Man in Black, Cash said his black clothing symbolised the downtrodden people in the world. Cash had been The Man in Black since he joined Nashville's famous radio variety show, the Grand Ole Opry, at age 25.
Cash won 11 grammy awards and
recently won an MTV music award
He won 11 Grammys, most recently in 2003, when Give My Love To Rose earned him honours as best male country vocal performance, and numerous Country Music Association awards.
He was elected to the Country Music Hall of Fame in 1980 and inducted into the Rock and Roll Hall of Fame in 1992.
Most recently, Cash was recognised for his cover of the Nine Inch Nails song Hurt with seven nominations at last month's MTV Video Music Awards.
He had hoped to attend the event but couldn't because of his hospital stay. The video won for best cinematography.
He also wrote books including two autobiographies, and acted in films and television shows.
John R Cash was born 26 February 1932, in Kingsland, Arkansas, one of seven children. When he was 12, his 14-year-old brother and idol, Jack, died after an accident while sawing oak trees into fence posts.
The tragedy had a lasting impact on Cash as he later pointed to it as a possible reason his music was frequently melancholy.
Cash once credited his mother, Carrie Rivers Cash, with encouraging him to pursue a singing career.
"My mother told me to keep on singing, and that kept me working through the cotton fields. She said God has his hand on you. You'll be singing for the world someday."