The former American footballer became a Hollywood action movie and comedy star, playing nemesis-turned-ally Apollo Creed in the Rocky movies.
Matt Luber, his manager, said Weathers died on Thursday. His family said he died "peacefully in his sleep".
As comfortable flexing his muscles on the big screen in Action Jackson as he was joking around on the small screen in shows like Arrested Development, Weathers was perhaps most closely associated with Creed, who made his first appearance as the cocky, undisputed heavyweight world champion in 1976's Rocky, starring Sylvester Stallone.
"It puts you on the map and makes your career, so to speak," he told The Daily Beast in 2017.
"But that's a one-off, so you've got to follow it up with something. Fortunately those movies kept coming, and Apollo Creed became more and more in people's consciousness and welcome in their lives, and it was just the right guy at the right time."
Most recently, Weathers has starred in the Disney+ hit The Mandalorian, appearing in all three seasons.