Clemons was taken to hospital about a week ago after suffering a stroke at his home in Singer Island, in the US state of Florida.
Known as the Big Man for his 6ft 5in frame, Clemons was credited with shaping the early sound of The Boss.
His solos powered Springsteen hits such as Born to Run and Jungleland.
Springsteen spokeswoman Marilyn Laverty confirmed the death on Saturday.
Clemons (left) and Springsteen worked together for nearly 40 years On his website, Springsteen said the loss of Clemons was "immeasurable" and that he and his bandmates were honoured to have stood beside him for nearly four decades.
The statement said: "Clarence lived a wonderful life. He carried within him a love of people that made them love him."
It added: "He loved the saxophone, loved our fans and gave everything he had every night he stepped on stage."
Canadian rocker Bryan Adams expressed his sadness via Twitter: "RIP Clarence Clemons, one of the greatest rock sax players."
Outside The Stone Pony, the legendary Jersey shore rock club where Clemons, Springsteen and other E Street band mates started out, fans have been leaving tributes since Clemons' death was announced.
The club will open its doors at noon on Sunday to let fans gather and reminisce.
Clemons had suffered from poor health in recent years, including major spinal surgery in January 2010.
At the 2009 Super Bowl, following double knee replacement surgery, he rose from a wheelchair to perform with Springsteen.
In May this year Clemons, a former youth councillor, was well enough to perform with Lady Gaga on the finale of the television show American Idol.
Football dreams
Born in Norfolk, Virginia, Clemons began playing saxophone at the age of nine after receiving one unexpectedly from his father for Christmas.
"I wanted an electric train for Christmas, but he got me a saxophone. I flipped out," he told the Associated Press news agency in a 1989 interview.
After his dreams of being a football player were dashed by a car accident, he turned to music.
Clemons hit it off immediately with Springsteen, then a singer-songwriter from New Jersey, when they first met in 1971, and the saxophonist became an original member of the E Street Band.
Their friendship survived Springsteen's decision to concentrate on solo projects following the success of his album Born in the USA.
In a 2009 interview, Clemons described his deep bond with The Boss, saying: "It's the most passion that you have without sex."
As well as TV and movie appearances over the years, Clemons performed with the Grateful Dead, the Jerry Garcia Band, and Ringo Starr and his All Starr Band.
He also recorded with legendary musical artists such as Aretha Franklin, Roy Orbison and Jackson Browne.
And he jammed with former US President Bill Clinton at the 1993 inaugural ball.
Clemons published a memoir, Big Man: Real Life and Tall Tales, in 2009.
The saxophonist once described performing as his natural environment.
The stage, said the Baptist minister's grandson, "always feels like home - it's where I belong".
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