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David Gill leaves his post as chief executive but will remain a director of Manchester United Football Club.
He joined the board in February 1997 as finance director and has been its chief executive since September 2003.
Executive vice chairman Ed Woodward will assume his responsibilities.
Announcing his departure, David Gill said; "It has been the greatest privilege to serve Manchester United for 16 wonderful years – the last 10 of which as its chief executive. I have worked alongside the finest manager in the history of the game and been part of what I consider to be the best club in the best sport in the world."
"It has been a very hard decision because I love this club and, as the fans’ banner says, it is, ‘more than a religion’", Gill added. "I’ve experienced some incredible highs, such as the Treble in 1999 and the League and Champions League double in 2008, and lows, like losing the title with the last kick of the season last year. But that is what makes this club and this sport so compelling."