Ole Gunnar Solskjaer’s men have tended to respond well to setbacks, but his inconsistent side faltered under the floodlights on Wednesday as their challenging season continued.
Just 25 days after United won 2-0 at Turf Moor, Burnley won by the same scoreline as Chris Wood and hometown hero Rodriguez netted either side of half-time to send United into a tailspin.
The majority of Old Trafford was on its feet when chants of “stand up if you hate Glazers” echoed around the ground following the Clarets’ second of the evening.
The owners and executive vice-chairman Ed Woodward were subjected to many other chants on a miserable night for United, whose injury-hit side flailed after a promising start as the need for January reinforcements was laid bare.
As for Burnley, this night will live long in the memory.
They had failed to win at Old Trafford since September 1962, but a stunning Rodriguez strike followed Wood’s fine opener as Sean Dyche got the better of United for the first time.
Burnley’s cheers mixed with United jeers at the end of a night that had started promisingly enough for the hosts.
Fred and Andreas Pereira had early half-chances, with Anthony Martial wasting a fine opportunity in the 16th minute when failing to make a telling connection to an Aaron Wan-Bissaka cross.
Diminutive Daniel James rose highest to meet another ball from the right-back with a header that Nick Pope saved, with the Burnley goalkeeper also denying Fred before a wonderful Charlie Taylor tackle thwarted hesitant Martial.
Burnley were creating little and Dyche had heated-looking words for Wood on the touchline. The New Zealand international headed a close-range effort wide soon after and managed to put a smile on his manager’s face in the 39th minute.
Ben Mee rose highest to nod on a diagonal free-kick into the box, with Wood getting ahead of Harry Maguire and firing past David De Gea. The world’s most expensive defender not only lost his man but played him onside.
Pereira led the attempts to level before the break but did not return for the second half as Mason Greenwood got the nod in a bid to change the dynamic of the match.
But 11 minutes after the restart, Burnley crushed United’s hopes – and darkened the mood within Old Trafford.
Rodriguez played a smart one-two with Wood and continued to hit a thumping left-footed drive that beat De Gea and went in off the underside of the bar in front of the Stretford End.
“We want United back” chants soon started, with fans getting on their feet as their displeasure at the Glazer family was made loud and clear.
Anti-Glazer and Woodward songs were bellowed out with renewed gusto as United attempted to turn things around.
James went close with a curling attempt and Mata sent a free-kick over after Taylor brought down Greenwood on the edge of the box. Video assistant referee Graham Scott decided against a red card for the left-back after reviewing the incident.
Martial was trying to force a goal as the match entered the closing stages, with Greenwood driving wide and Luke Shaw seeing a 90th-minute consolation headed goal ruled out for a foul – a decision the VAR agreed with.