Simpson was a running back for the Buffalo Bills and San Francisco 49ers, before being acquitted of murder in a trial in the mid-1990s and later served jail time for an armed robbery.
His children announced the news of his death on X, saying: "On April 10, our father, Orenthal James Simpson, succumbed to his battle with cancer.
"He was surrounded by his children and grandchildren. During this time of transition, his family asks that you please respect their wishes for privacy and grace. -The Simpson Family."
After he retired from the NFL in 1979, an acting career beckoned, with Hollywood moguls beating a well-worn path to his door.
On April 10th, our father, Orenthal James Simpson, succumbed to his battle with cancer.— O.J. Simpson (@TheRealOJ32) He was surrounded by his children and grandchildren. During this time of transition, his family asks that you please respect their wishes for privacy and grace.-The Simpson FamilyApril 11, 2024
He became one of the TV glory boys as a commentator and then an actor in films.
A young Simpson was among the supporting cast of 1976 thriller The Cassandra Crossing, making his way from American football star to movie hero.
He got the part after it was turned down by James Coburn.
Simpson also featured in the 1989 comedy film The Naked Gun: From the Files Of Police Squad! - which also starred Leslie Nielsen, Priscilla Presley and George Kennedy.
He revisited his role as a detective sidekick in the Naked Gun follow-ups The Smell Of Fear and The Final Insult.
Simpson also appeared in 1974 drama The Klansman, disaster film The Towering Inferno and starred in his own hidden-camera prank TV show Juiced With OJ Simpson.
Simpson was acquitted of the murder of his former wife Nicole Brown Simpson and her friend Ron Goldman in 1995.
Famously, Kim, Kourtney and Khloe Kardashian's father Robert Kardashian was a member of Simpson's defence team.
He was later jailed following an armed robbery in Las Vegas in 2007 and served a lengthy sentence before being released in 2017.
He was discharged from parole in December 2021.
The People V OJ Simpson: American Crime Story - which aired in 2016 - won a number of Emmys for its portrayal of the murder trial of the former NFL star.
It starred Sarah Paulson and Cuba Gooding Jr as Marcia Clark and OJ Simpson respectively in the 10-part dramatisation of the trial that mesmerised the world in 1994.
The series also starred Sterling K Brown, John Travolta, Friends star David Schwimmer and Kenneth Choi.
The car chase that led to Simpson's arrest and the subsequent trial were televised live and were media sensations.
Speaking on the red carpet in 2016, Gooding Jr said: "I remember watching the Knicks game and then turning it to the chase and putting the game on the radio and listening to it, but watching the chase so we didn't miss anything crazy.
"I played this character to some degree before in Jerry Maguire, I studied these flamboyant marquee athletes and I believe that there is something about their personalities when they are young and show that special skill that they get shielding from social interaction so when their career is over they still have that infantile frame of mind so that motivated a lot of my performance."
Travolta, who played Simpson's defence lawyer Robert Shapiro, said: "It's probably the most prominent celebrity crime story that ever happened. It was part of our American history with our favourite sport."
Schwimmer, who played Robert Kardashian, said the elements in the case created a perfect storm.
"There were so many factors that went into this tragic story, it's almost at the level of a Greek myth, of this incredible icon and his fall from grace," he added at the same 2016 event.
"More than that it was about sex and race and politics and celebrity, unfortunately or not it had everything that we are morbidly fascinated by."
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