An inspired Wayne Rooney became Manchester United's all-time leading goalscorer in European competition to ignite their crucial 4-0 trouncing of Feyenoord.
Inter Milan's calamitous season hit a new low on Thursday as they squandered a two-goal lead to lose 3-2 at Israeli club Hapoel Beer-Sheva and suffer the embarrassment of an early Europa League exit.
After one of European football's giants capitulated, another flexed their muscles with an inspired Wayne Rooney becoming Manchester United's all-time leading goalscorer in European competition to ignite their crucial 4-0 trouncing of Feyenoord.
For a while, it seemed the struggling Italian giants Inter, who had begun the night propping up Group K and had to win to survive, would be given a reprieve thanks to first-half goals from Mauro Icardi and Marcelo Brozovic.
Yet in keeping with a season in which they had already sacked manager Frank de Boer and fans had turned on captain Icardi for his comments about them in his autobiography, everything started to go wrong after the break.
Hapoel, who had caused a sensation by winning at the San Siro in their opening group match, pulled one back with a header from Lucio Maranhao before Inter keeper Samir Handanovic was shown a second yellow in conceding a penalty that Anthony Nwakaeme converted.
Scenting another famous win, the Israelis poured on the pressure against 10 men and, in the 93rd and final minute, Ben Sahar slotted home a cool finish after one last slick attack.
The latest setback left Inter down and out on three points but breathed fresh hope into Hapoel, who moved on to seven points alongside second-placed Southampton, who blew their chance of qualifying in the penultimate round with a 1-0 defeat at Sparta Prague.
Sparta earned their passage into the knockout stages thanks to an 11th minute goal from their Zimbabwean defender Costa Nhamoinesu. It was the first time in nearly 33 years that the Czech club had downed top-flight English opponents.
The drama sets up a winner-takes-all final group match between Southampton and Hapoel for the second spot.
It was a landmark night for England captain Rooney at Old Trafford as he netted his record-breaking 39th European goal that took him past Ruud van Nistelrooy's milestone of 38 and left his side well-placed to progress to the last 32 from Group A.
It has been a difficult period for Rooney, who had apologised for being pictured late at night at a wedding party while on international duty before then complaining that he had suffered "disgraceful" treatment from the media.
Having trumpeted that he was "not yet finished", the 31-year-old was as good as his word, with an exquisite first-half chip putting United ahead and a lovely pass after the break setting up Juan Mata for their tap-in second.
Feyenoord goalie Brad Jones then parried Zlatan Ibrahimovic's cross into his own net and Jesse Lingard completed the rout as United leapfrogged the Dutch side to take second place in the table, leaving them requiring just a point at Zorya Luhansk to guarantee progress.
Asked if his achievement felt more special after his recent dramas, Rooney told BT Sport: "All that's created by people like yourself asking questions like this. People in the media are making a big deal over nothing.
"I think it's a shame I have to be talking about it now after such a great victory."
Leaders Fenerbahce had earlier put pressure on United in Group A with their 2-0 win over Ukraine's Zorya in Istanbul, Miroslav Stoch and Simon Kjaer scoring in the space of eight minutes midway through the second half.
FK Qarabag's hopes of becoming the first team from Azerbaijan to qualify from the group stages of a UEFA competition were still alive despite being hammered 3-0 at Slovan Liberec, with Nikolai Komlichenko scoring twice.
With PAOK Salonika striking in the 93rd minute through Garry Rodrigues to snatch a dramatic 3-2 win at Fiorentina after the Italian side had come from two down and were seconds away from claiming a place in the knockout stages, there is still everything to play for in Group J.
Fiorentina, leading on 10 points, visit second-placed Qarabag in their final game with the Azeris on seven points, the same tally as Salonika, who will host Liberec.