Ed Woodward has stepped down as executive vice-chairman of Manchester United.
The move comes amid fury at plans to create a European Super League featuring six English teams, including Manchester United, and other top clubs from Spain and Italy.
All Premier League clubs involved in the ESL – Arsenal, Chelsea, Liverpool, Manchester City, Manchester United and Tottenham – have now pulled out of the breakaway competition.
It leaves just Atletico Madrid, Barcelona, Real Madrid, AC Milan, Inter Milan and Juventus still involved.
Mr Woodward, 49, took the job at Old Trafford in 2013 and played a key role in the controversial project.
He had been singled out for criticism over the new league by the head of UEFA, Aleksander Ceferin.
Mr Woodward had already agreed to leave the post at the end of this year, but the announcement has been brought forward, according to Sky Sports News.
It is understood he will continue in his role with United until the end of 2021.
He said in a statement: "I am extremely proud to have served United and it has been an honour to work for the world’s greatest football club for the past 16 years.
"The club is well positioned for the future and it will be difficult to walk away at the end of the year.
"I will treasure the memories from my time at Old Trafford, during a period when we won the Europa League, the FA Cup and the EFL Cup.
"I desperately wanted the club to win the Premier League during my tenure and I am certain that the foundations are in place for us to win it back for our passionate fans."
He was an unpopular figure with fans during a period at United that saw some very expensive signings but precious little success.
Co-chairman Joel Glazer had hailed the Super League a "new chapter" despite widespread condemnation.
Players, pundits and politicians earlier praised Man City and Chelsea for their decision.
Prime Minister Boris Johnson tweeted: "The decision by Chelsea and Manchester City is – if confirmed – absolutely the right one and I commend them for it. I hope the other clubs involved in the European Super League will follow their lead."
Culture Secretary Oliver Dowden added: "Good news that Chelsea and City have seen sense, and I urge the rest to follow swiftly.
"The whole ESL move shows how out-of-touch these owners are. They have completely misjudged the strength of feeling from fans, players and the whole country. Football is for the fans."