"John has mutually agreed with us that now is the right time to step aside and allow the new football leadership structure to be put in place," Manchester United co-chairman Joel Glazer said.
The announcement comes months after British billionaire Jim Ratcliffe took control of football operations at the Premier League club with his acquisition of a 25 per cent stake for $1.25 billion (£987 million).
The American Glazer family retains a majority stake in the club.