Born John Weatherspoon, he started out as a stand-up comedian in the 1970s.
He made his film debut in the 1980 The Jazz Singer and appeared in Hollywood Shuffle, Boomerang, Vampire in Brooklyn and The Ladies Man.
The cause of death is not known. Relatives and celebrity friends have been paying tribute to Witherspoon.
"We love you 'POPS' always and forever," his family said on his Twitter account.
He voiced the grandfather in the Boondocks animated series and was a frequent guest on Late Show with David Letterman
But for many, Witherspoon's performance as "Pops" in Friday was his most recognisable role. He also appeared in the sequels Next Friday and Friday After Next.
Ice Cube said in a Twitter post he was devastated by the death. "Life won't be as funny without him," he added.
Celebrities including Chance The Rapper, actress Jackée Harry, director Judd Apatow and Ava Dupernay paid tributes to the actor.