Manchester United's Europa League hopes suffered a major setback as they were beaten 2-1 by Fenerbahce in Istanbul.
The home side were ahead after just 69 seconds through Moussa Sow's brilliant overhead kick and things got even worse for the visitors when Paul Pogba left the field in the 29th minute after picking up a knock.
United dominated possession but could not find a way through Fenerbahce's stubborn defence, and they were punished in the 59th minute when Jeremain Lens - on loan with the Turkish side from Sunderland - beat David de Gea with a spectacular free-kick.
Wayne Rooney pulled a goal back in the 89th minute with a superb long-range effort to score a record-equalling 38th goal for United in Europe, but Dick Advocaat's side held on to take all three points and move above Jose Mourinho's team to the top of Group A after Feyenoord's 1-1 draw at Zoyra.
Fenerbahce left former United striker Robin van Persie on the bench with Advocaat opting for Sow in his place and the Dutchman's decision was justified with less than two minutes on the clock.
Hasan-Ali Kaldirim whipped the ball into the United penalty area from the left and Sow produced a moment of brilliance, connecting with a stunning over-head kick to loop the ball over De Gea and into the back of the net from 18 yards.
The goal raised the roof at the Sukru Saracoglu Stadium but United responded with plenty of possession as Fenerbahce looked to hit the visitors on the counter-attack.
Lens looked a real threat down the left and he was hauled down just outside the penalty area by Morgan Schneiderlin.
The free-kick came to nothing but then United started to get a grip of proceedings with Anthony Martial picking out Rooney in the penalty area, but the England captain's touch let him down at the crucial moment.
United were forced into a re-shuffle on 29 minutes because of an injury picked up by Pogba. The France midfielder limped heavily after a challenge and eventually trudged off to be replaced Zlatan Ibrahimovic.
The Swedish striker was straight into the action and he was fortunate that his altercation with Simon Kjaer was missed by officials as tempers frayed towards the end of the first half.
With United chasing the game, Mourinho sent on Juan Mata for Schneiderlin at the break and they continued to dominate possession without creating any clear-cut chances.
Martial looked to provide the creative spark for United, curling a ball into the box towards Rooney, but he could only glance his header wide of the far post.
Mata then flashed a shot wide as the visitors looked to build pressure on Fenerbahce, but Lens added to United's problems in the 59th minute with a superb free-kick after referee Milorad Mazic ruled that Ibrahimovic fouled Mehmet Topal.
United continued to have the majority of the ball, but the hosts could have extended their lead with substitute Emmanuel Emenike forcing De Gea into a smart save.
The match looked to be petering out into a comfortable Fenerbahce win until the 89th minute when Rooney found the top corner with a wondrous drive to equal Ruud van Nistelrooy's European record.
It led to a frantic finale but Fenerbahce held out to secure a memorable victory that sees United drop out of the Group A qualification spots with two games remaining.