The Red Devils were beaten 1-0 on the night and 2-1 on aggregate by Atleti, with Renan Lodi's first half header succumbing United to an early exit.
United had drawn 1-1 in Madrid in the first leg thanks to Anthony Elanga's late strike cancelling out Joao Felix's header.
With no away goals, they needed to be on the front foot at Old Trafford and play for the win.
And while there was plenty of intensity and possession from the hosts, they could not find a way through Diego Simeone's stern side.
Atleti, meanwhile, needed just the one goal on the night but it wasn't without controversy. United complained strongly about two possible fouls in the build up to the winner - one on Elanga and one on Fred in the same passage of play.
REGARDEZ FRED A 0:07 COMMENT IL SE FAIT HAGAR ET L’ARBITRE DIT RIEN pic.twitter.com/LRQlI9ML7n— Aïssa🇨🇲🇩🇿 (@IMISSUAISSA__91) March 15, 2022
The La Liga champions countered wonderfully and with United's backline all over the place, Antoine Griezmann picked out Lodi at the far post.
A brief VAR check was held but the goal stood and having failed to reply, United have now suffered more Champions League misery.
What's more, it means they have now extended their trophyless period to six seasons.
The last bit of silverware for United was the Europa League win under Jose Mourinho in 2017.
Featured Image Credit: Image: PA
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