United's miserable European home form continued as they were completely outplayed by Bilbao at Old Trafford on Thursday night.
The Red Devils have now managed just one win in five games on home turf in the Champions League and Europa League this season, including two defeats on the trot after the Basque outfit overturned Wayne Rooney's first-half strike and then withstood a late United rally that brought the England forward his second goal, from the penalty spot.
Fernando Llorente capped an outstanding performance with the equaliser before Oscar de Marcos put the visitors ahead and Rafael's woeful defending allowed Iker Muniain to grab a third.
A combination of Rooney's goals and a defiant display from David de Gea ensured United are not out of it yet.
Even so, it would take a quite remarkable change in fortunes for United to turn this tie on its head in Bilbao next week.
It only took a quick look at Athletic's form this season to work out if they were taking the tie seriously, United's credentials were in for a fairly testing examination.
A noisy travelling support of around 7,000 ensured the visitors' minds were focused despite the twin attractions of competing for a place in next season's Champions League and a forthcoming Copa del Rey final showdown with Barcelona.
Llorente quickly established himself as Athletic's dangerman, his muscular frame providing a battering ram of a problem for United's defence.
Twice the burly front-man went close in the opening stages, nodding over before curling a shot just wide.
Markel Susaeta impressed in support and he came close to providing a magnificent riposte to Rooney's opener when he outpaced Jonny Evans to reach Javi Martinez's lofted pass, lobbing De Gea with a first-time effort which bounced narrowly wide.
No-one could begrudge Athletic their equaliser when it arrived two minutes before the break, although Sir Alex Ferguson would doubtless complain at the simplicity of it.
Llorente fed the ball out wide on the edge of the area, then spun and bulldozed his way to the six-yard box, where Susaeta's cross was perfectly timed.
It rather punctured the optimism Rooney had created with his clinical effort.
In truth, Ryan Giggs deserved some of the plaudits for his deft pass and Javier Hernandez even more due to the Mexican's nimble feet, which took him past Martinez and allowed the shot that Gorka Iraizoz could only parry into Rooney's path.
It was a significant goal in the sense it took the striker level with Denis Law on 28 European goals, a tally that leaves him just one behind Ryan Giggs and 10 adrift of Ruud van Nistelrooy, United's top scorer in continental combat.
If United thought they had endured the best Athletic could do, they were mistaken.
From an acute angle, Muniain managed to fire through a crowd of bodies, forcing De Gea to repel at full stretch.
It was the start of an impressive stint of attacking play from Athletic.
Llorente blasted into the side-netting, then was denied by De Gea after escaping the rather lax attentions of Rafael.
Amid all this, the Red Devils lost Chris Smalling - whose head wound suffered on international duty last week reopened to leave blood running down the side of his head.
Ferguson had enough to worry about without having the substitutes' replacement board being dropped on him by assistant Rene Meulensteen.
Castigated a couple of months ago, De Gea impressed, denying Muniain again after Herrera had found him with a fabulous return pass.
Given how the game had gone, it would have been churlish to make too much of the fact Athletic's second goal should have been ruled out for offside.
United's defence was torn to shreds by some intricate one-touch passing that ended with Herrera lifting the ball up for De Marcos to run onto.
In an instant, the ball was nestling in the net, and fully deserved it was too.
There was more late drama though as Rafael's shocking defending, after De Gea had saved another De Marcos shot, allowed Muniain to blast into an empty net.
United were in deep trouble, only for Rooney to move level with Giggs and more importantly provide some hope with an injury-time penalty after De Marcos had handled.