The mightily-frustrating goalless draw at home to Burnley was followed by news that the Portuguese's behaviour towards the officials on Saturday would not only dent his wallet but see him banned from the touchline at Swansea this weekend.
Those issues were compounded on Thursday night as United failing to win a seventh straight European away match, with Fenerbahce deservedly winning 2-1 as the visitors failed to add to Rooney's late stunner.
The captain's strike saw him equal Ruud van Nistelrooy's record as United's all-time European top scorer, but it was too late to spur a comeback in a match that was just 65 seconds old when Moussa Sow scored with a superb overhead kick.
Fenerbahce's players, helped by the baying Sukru Saracoglu Stadium crowd, continued to make life uncomfortable for United, who lost world-record signing Paul Pogba after 30 minutes following a heavy challenge.
Zlatan Ibrahimovic was fortunate that his altercation with Simon Kjaer was missed by officials as tempers frayed, with Jeremain Lens, on loan from Sunderland, adding to United's problems with a superb second-half free-kick.
Rooney's wondrous 89th-minute drive led to a frantic ending, but Fenerbahce held out to secure a memorable victory that sees them usurp United in the Group A qualification spots.
The intimidation aspect played a part from the outset. A cacophony of noise greeted United at the warm-up and it only increased as kick-off approached, with the emotions peaking within 65 seconds.
Hasan Ali Kaldirim floated in a cross from the left and could not have foreseen Sow meeting it with such an exceptional overhead kick, beating David de Gea to send the Fenerbahce support wild.
It was a sucker punch similar to that dealt at Stamford Bridge recently when Chelsea dished out a 4-0 shellacking, so United were relieved to see Souza miss the target with a header after being left unmarked from a free-kick soon after.
Morgan Schneiderlin, one of United's alterations, was booked for the clumsy challenge that led to that free-kick and Ander Herrera soon joined him in the referee's notebook, just days after being sent off for two against Burnley.
Mourinho's side were looking shaky without the ball and struggling to create chances when they had it, with Marcus Rashford's wayward strike across goal the best they could muster in the opening 20 minutes.
Rooney would have been through had an awful touch not seen a clever Anthony Martial ball go to waste, with Pogba showing a lovely touch but poor finish before succumbing to a leg injury.
The France midfielder limped heavily after a heavy challenge and trudged off after 30 minutes, with Lens wasting a counter-attack before Ibrahimovic could be brought on.
His introduction brought a spell in the ascendancy and only goalkeeper Volkan Demirel's intervention prevented Rashford's low cross being turned home by the veteran striker.
Ibrahimovic also brought an added spice to the match, grabbing Kjaer by the neck to establish himself as persona non grata with the Turkish supporters.
Rooney also irked the home faithful having been infuriated by the way Souza threw himself to the deck, leading the teams to clash as the fans were further antagonised.
Juan Mata replaced Schneiderlin as United returned from the break strongly.
Rooney, playing in a deeper position, glanced a header just wide of the right-hand post, which Mata just evaded with a snap shot.
Fenerbahce, though, were playing smartly and winning free-kicks whenever they could.
United could not believe referee Milorad Mazic ruled that Ibrahimovic had fouled Mehmet Topal and were even more shocked to see Lens superbly bend home the resulting free-kick.
It was an exceptional goal that substitute Emmanuel Emenike could have added to.
The former West Ham loanee could not beat De Gea having been unsteadied by Daley Blind, before forcing the Spaniard into a save from distance and then just missing a low cross.
The match looked to be petering out until Rooney wound back the years, rifling home a stunning strike from distance.
It led to a frantic ending as a timely block was followed by one that United felt should have led to a penalty, with handball appeals against Martin Skrtel from Herrera's shot.
Elsewhere in Thursday's early evening kick-offs, League of Ireland champions Dundalk were beaten 2-1 away at Group D leaders Zenit St Petersburg.
Giuliano had put the Russians in front on 41 minutes, but Daryl Horgan's goal - following a swift counter-attack - levelled matters on 52 minutes.
Zenit, though, maintained their 100 per cent record when Brazilian Giuliano netted again with 22 minutes left.
The game between Maccabi Tel-Aviv and AZ Alkmaar ended goalless, meaning Dundalk retain second place in the table.
Aritz Aduriz scored all the goals as Athletic Bilbao beat Genk 5-3 to open up the qualification race in Group F, the striker completing his impressive haul in stoppage time with what was a hat-rick of penalties.
Sassuolo remain top after they drew 2-2 at home against Rapid Vienna, who scored a late equaliser - but now all four teams are separated by just one point.
Roma won 4-2 at Austria Vienna with a brace from Edin Dzeko to climb to the top of Group E, with the other tie ending 1-1 between Astra Giurgiu and Viktoria Plzen.
Apoel Nicosia lead Group B after the Cypriots beat Swiss side Young Boys 1-0 and Olympiakos drew 1-1 away to FC Astana.
Anderlecht thumped Mainz 6-1 in Group C, where French team St Etienne, continued their qualification push with a 2-1 win at Qabala, who have yet to register a point.
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