News of his death was confirmed to AFP by his publicist on Friday.
Although he suffered from colon cancer, Chadwick Boseman never publicly discussed his condition and kept the matter private.
He spent his time working on major Hollywood movies during and between “countless” operations and chemotherapy, according to a statement by his family.
"It was the honor of his career to bring King T'Challa to life in 'Black Panther'," they said.
"A true fighter, Chadwick persevered through it all," the statement added. He died in his home "with his wife and family by his side", it said.
Boseman played the first black superhero to get his own standalone film in the record-breaking Marvel franchise with 2018's "Black Panther".
The movie, set in the fictional African kingdom of Wakanda, was adored by critics and audiences, becoming the first comic book film to be nominated for best picture at the Oscars and grossing over $1 billion worldwide.
Earlier in his career, Boseman played black icons Jackie Robinson in "42" — Friday, ironically, was Jackie Robinson Day in the US — and James Brown in "Get on Up".