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The executive vice-chairman will be replaced by new chief executive officer Richard Arnold, the club have announced.
Woodward revealed his intention to walk away from his post after last year’s failed attempts to create a European Super League.
United were one of the key figures in the breakaway competition that was quickly abandoned after widespread condemnation from supporters and the sport at large.
Woodward has been a controversial chief since taking over the reins in the wake of Sir Alex Ferguson’s retirement in 2013.
Under his watch, United went from the dominant force in English football to a side that has frequently failed to secure top-four finishes.
They have not won the title since Ferguson’s departure and watched as fierce rivals Manchester City and Liverpool have overtaken them as the country’s leading clubs.
Under Woodward, United only won three major trophies - the FA Cup, the Carabao Cup and the Europa League. The departing chief was often criticised by fans for United’s failures on the pitch and their transfer record.
But he did secure a host of major signings including the world-record £89million deal for Paul Pogba and the return of Cristiano Ronaldo. Yet it has been United’s decline on the pitch that will define his tenure.
Ole Gunnar Solskjaer became the fourth managerial sacking under his watch in November and he leaves the club in a state of uncertainty, with interim Ralf Rangnick only in place until the end of the season.
Arnold was one of Woodward’s key allies and steps up from group managing director in a move that supporters may fear will see little change in the direction of the club under the ownership of the Glazers.