The Tampa Bay Buccaneers, the American football club which he owned since 1995, announced the news on its website.
It said it was “saddened” to announce Mr Glazer had passed away this morning at the age of 85.
He leaves behind his wife Linda, six children and 14 grandchildren.
Mr Glazer, who lived in Palm Beach, Florida, bought Manchester United in 2005.
Since then, the football club won five Premier League titles (2007, 2008, 2009, 2011 and 2013), as well as the 2008 Champions League title.
The Buccaneers described him as a “pioneering thinker” and “dynamic business leader” who “rebuilt the Buccaneers into a model franchise and a Super Bowl winner”.
It added: “Known among his league peers as a pioneering thinker, Glazer infused his team and employees with the determination and dedication to be the best in the NFL.
“Glazer’s commitment to building a championship organisation has provided the foundation for continued success, on and off the field.”