A strike from £31m forward Memphis Depay gave United a crucial away goal before Midtjylland, who were only formed in 1999, stormed back to claim the most famous victory in their history with goals from Pione Sisto and Paul Onuachu.
Premier League defeat at Sunderland on Saturday cast United six points adrift of a Champions League place and left qualification for next season’s elite European club competition in grave doubt.
Winning the Europa League is perhaps United’s best avenue into the Champions League next term and while a 1-0 victory in next week’s second leg would prove sufficient to progress to the last-16, their future in the tournament is in the balance.
“It is the law of Murphy, I think,” said former Holland manager Van Gaal, who was forced to name Sergio Romero as United’s goalkeeper after David de Gea was sidelined with a knee injury in the warm-up.
“When you start a game and your goalkeeper is No14 on the injury list then you are not starting like usual. A lot of things are happening in the heads of the players. The first goal is deflected, it is unbelievable, it is too much.”
Depay’s close-range finish from Jesse Lingard’s cross was cancelled out before half-time by Sisto, whose shot deflected off the shins of England centre-half Chris Smalling. Substitute Onuacho’s low shot from the edge of the penalty area, after he easily brushed aside Juan Mata, in the 77th minute proved Midtjylland’s winner.
Ex-West Ham midfielder Michael Carrick, United’s stand-in skipper after Wayne Rooney was ruled out for six weeks with a knee ligament injury, refused to pull any punches: “It’s not good enough, not acceptable. The performance is nowhere near good enough.”