Man City were the clear favourites having been crowned Premier League champions for an unprecedented fourth consecutive season last weekend.
United finished eighth in the table and knew victory in the FA Cup represented their last chance of qualification for European football next season.
Even more damning reports suggested that a United defeat could be the end for manager Erik ten Hag who is facing increasing pressure following an underwhelming season.
However, Man United threw the form books out of the window when Alejandro Garnacho capitalised on a Man City blunder to hand the Red Devils the lead at the half-hour mark.
Youngster Kobbie Mainoo doubled the advantage for Ten Hag’s men nine minutes later to send United fans into cloud nine.
Much of Manchester United’s strategy in the second half was protecting that two-goal lead and they followed it perfectly until Jérémy Doku struck to reduce the deficit three minutes from time.
Manchester City tried all they could to find a late equalise but Pep Guardiola’s men faltered when it mattered most allowing United to secure a memorable win.
It is the second title win of Erik ten Hag’s spell at Man United after he guided the club to Carling Cup triumph last season.