Ed Woodward is understood to have resigned as Manchester United executive vice-chairman.
The 49-year-old took the post at Old Trafford in 2013 and played a key role in the now stuttering European Super League. It is thought he will continue in his role with United until the end of 2021, according to the PA news agency.
The closure of the New York Stock Exchange is expected to bring confirmation of the executive vice-chairman's departure within the hour.
Woodward's exit is understood to be amicable with the owners and reportedly unrelated to the Super League.
Whatever the reasoning behind his exit, he becomes the first high-profile departure since the divisive breakaway league was launched less than 48 hours ago.
United were among six Premier League clubs to join the 12-strong European competition, with club co-chairman Joel Glazer hailing it as a "new chapter" despite widespread condemnation.
Glazer was named as vice-chairman of the Super League, but Uefa president Aleksander Ceferin took aim at United's chief executive Woodward.
"I didn't have much contact with him but he called me last Thursday evening, saying that he's very satisfied with the reforms, that he fully supports the reforms, and that the only thing he would like to speak is about financial fair play," he said of talk about the new-look Champions League. "And obviously he already signed something else."
Former United captain Gary Neville responded to the news of Woodward's departure by posting a waving emoji.
Woodward's decision to leave his position came after reports that Chelsea, Manchester City and Atletico Madrid were pulling out of the planned breakaway which has received intense criticism and opposition.
The soon-to-be former United chief was an unpopular figure with fans during a period that saw some big-money signings but precious little success.
Following Alex Ferguson's retirement as a champion in 2013, Woodward wielded the axe on David Moyes after a poor first season.
Successor Louis Van Gaal has a topsy-turvy time in charge and was sacked just days after winning the FA Cup in 2016 – the club's first major trophy since Ferguson retired.
Jose Mourinho came in, winning the League Cup and Europa League in his first term as United boss and leading them to the second in the Premier League in 2017/18.
But things unravelled and he was dismissed in December 2018, with Ole Gunnar Solskjaer brought in on an interim basis and impressing enough to get the job permanently.
The Norwegian has led United through to this season's Europa League semi-finals and second in the Premier League, putting them on course for back-to-back top-four finishes for the first time since Ferguson retired.
United's share price on the New York stock exchange fell to below its valuation before news of the ESL broke after a jump on Monday.