The Red Devils' woes continue with Thursday's defeat at the hands of the Turkish side, as Wayne Rooney's late goal failed to spark a comeback
Moussa Sow's sensational overhead effort and a brilliant free-kick from Jeremain Lens helped Fenerbahce to a fine 2-1 Europa League win over an out-of-sorts Manchester United, who lost Paul Pogba to injury.
Fener were swept aside in a 4-1 loss at Old Trafford a fortnight ago in a match that saw Pogba score twice.
But Jose Mourinho has faced increased scrutiny over United's indifferent Premier League form with a 0-0 draw at home to Burnley in which they registered 37 shots on goal at the weekend the latest disappointment.
And the Portuguese's mood would hardly have been helped by Sow's stunning acrobatic opener in just the second minute of the Group A contest in Istanbul that left left United with an uphill task.
The loss of world-record signing Pogba to injury shortly before half-time compounded United's misery, before Lens - on a season-long loan from Sunderland - rubbed salt in the wounds with a brilliant 59th-minute free-kick.
Captain Wayne Rooney reduced the deficit with a magnificent long-range goal of his own that drew him level with Ruud van Nistelrooy on the list of United's all-time leading goalscorers in Europe on 38.
But it did little to mask a limp, disjointed performance from United and they are now one point adrift of new pool leaders Fener and Feyenoord, who drew 1-1 at Zorya, with two group games remaining.
There was nothing United could do about Fener's spectacular opener, though.
Hasan Ali Kaldirim crossed from the left and Sow connected with a stunning overhead kick just inside the area that looped over David De Gea.
United struggled to create openings in their search for an equaliser and Morgan Schneiderlin was fortunate his crude challenge on Jeremain Lens occurred just outside the box.
Anthony Martial did carve open Fener's defence with a fine ball into the path of Rooney, but his touch was poor and Martin Skrtel cleared the danger.
United were then forced into a premature change when Pogba, who had earlier taken a strong challenge from Souza, hobbled off to be replaced by Zlatan Ibrahimovic.
The visitors continued to toil and emotions almost boiled over towards the end of the half with Ibrahimovic involved in a coming together with Simon Kjaer, while Fener goalkeeper Volkan Demirel took exception to a Rooney challenge on Souza.
Fener were happy to sit back in the second half and allow United to dictate possession and the visitors appeared devoid of ideas, with a glancing Rooney header all they had to show for their efforts.
And the hosts' approach paid dividends shortly before the hour when Lens curled an excellent 25-yard free-kick into the bottom right-hand corner past a helpless De Gea.
United were fortunate the game was not beyond all doubt when substitute Emmanuel Emenike sprung the offside trap to collect Lens' throughball, his heavy touch allowing De Gea to make the save.
Rooney forced a nervy ending by picking out the top-left corner from almost 30 yards, but Fener held out for the points.