With the triple European Cup winners already immersed in a pall of gloom after a hugely underwhelming campaign, their best hope of returning to the Champions League next season is now in peril.
Borussia Dortmund and holders Sevilla were among the high-profile clubs to secure comfortable wins as the Europa League's knockout stages got underway but United were undone in the 77th minute by a goal from Paul Onuachu.
The substitute pinched the ball after a half-hearted challenge from Juan Mata on the edge of the area and swivelled before firing home a low bouncing drive to earn the Danes victory.
United had started positively and went ahead in the 37th minute with a scrappy goal from Memphis Depay.
The advantage was cancelled out a minute before halftime when Pione Sisto pounced on a mistake from Michael Carrick and scored with a low shot.
Tottenham Hotspur secured a priceless away goal and a 1-1 draw at Fiorentina in one of the evening's more glamorous ties while Villarreal overcame Napoli 1-0 in Spain.
Sevilla's grip on the trophy showed no sign of loosening as their bid for a third straight triumph began with a 3-0 victory at home to Norway's Molde.
Fernando Llorente netted twice for the holders who, like United, were playing their first game in this season's competition having dropped into it after failing to reach the knockout rounds of the Champions League.
Sevilla, who beat Dnipro Dnipropetrovsk in the final in Warsaw in May, opened the scoring against Molde when Llorente fired a pinpoint effort into the net off the post 10 minutes before halftime.
The Spain striker doubled his tally when he held off his marker and blasted the ball into the roof of the net four minutes after the restart. Kevin Gameiro made it 3-0 by driving the ball beneath the Molde keeper.
Dortmund recorded a 2-0 win at home to Porto on a night when the fixture list had an alluring look.
So often derided as a poor cousin of the Champions League, Europe's second tier competition returned with a high-profile lineup including five former European Cup winners.
St Etienne beat Basel 3-2 and Anderlecht downed Olympiakos Piraeus 1-0 in the remaining early matches.
Former European champions Liverpool and Olympique Marseille are among the sides involved in Thursday's later games. – Reuters
Original source: More woe for United, LVG