With United’s season all pinned on the Europa League, there was no exaggerating that this clash was all or nothing for Ruben Amorim’s men. And they started like a team with serious purpose, breaking the deadlock inside 10 minutes.
A through ball from Noussair Mazraoui released Bruno Fernandes down the right, and the captain picked out Alejandro Garnacho, whose pinpoint square ball was swept home by Manuel Ugarte.
The high press almost produced a quick second goal as Garnacho nicked the ball and picked out Casemiro, but the Brazilian’s strike was tipped around the post by Lucas Perri.
It took a while for Lyon to get going, with their first opportunity arriving midway through the half when Paul Akouokou’s header was brilliantly saved by the returning Andre Onana.
Rayan Cherki was growing in the contest as he glided through the United rearguard before firing on goal, but Onana once again dived down to his right to make the stop.
Fernandes then almost brought the house down with an audacious volley after being picked out by Diogo Dalot, only for the crossbar to deny him, before arrowing a long-range strike marginally wide.
Undeterred, United maintained their momentum and ended the half in perfect fashion, doubling their lead after Dalot controlled Harry Maguire’s crossfield pass before firing into the far corner.
The hosts picked up where they left off before the break and should have put the tie to bed within five minutes after Garnacho broke through on goal, but he dawdled on the ball and eventually hit straight at Perri.
Lyon had struggled to make an impact in the second half, but suddenly salvaged a lifeline to halve the deficit after United failed to clear a set-piece, which was headed on by Alexandre Lacazette and nodded home by Corentin Tolisso.
That goal sparked a change in momentum, and Les Gones needed just six minutes to draw level as Ainsley Maitland-Niles’ mishit cross was bundled over the line by Nicolas Tagliafico.
The pendulum swung again in the 89th minute when Tolisso was sent off, receiving a second yellow card for a trip on Leny Yoro. United didn’t have long enough to use that to their advantage, meaning extra time was required to determine a winner of the tie.
And despite being a man down, Lyon were the ones to step up after Cherki pounced on a loose ball on the edge of the box and lashed home.
United had no response and conceded again when Lacazette converted from the penalty spot after Luke Shaw felled Malick Fofana.
The Red Devils looked down and out, but were given a lifeline when Casemiro was felled in the box and Fernandes set up a grandstand finish, tucking the spot-kick past Perri.
And the big moment arrived in the 120th minute when Kobbie Mainoo showed great composure in the box to cut inside and finish into the far corner.
His makeshift strike partner Harry Maguire then popped up just a minute later to head home and blow the roof off Old Trafford.
A stunning finish to a spectacular tie sends United through to the semi-finals, where they will face Athletic Club.
Flashscore Man of the Match: Bruno Fernandes (Manchester United)