Ahead of tonight's match, Andy Mitten looks back at the meeting between the clubs in 1957.
United and Bilbao ushered in continental football for English teams
More than 6,000 Basques have congregated in Manchester for the first competitive meeting between the clubs since 1957, the largest European away following to descend on Old Trafford.
Whatever happens, this first leg of the last 16 stage of the European competition many in Britain rate as a booby prize will find it difficult to compete with the European Cup quarter-final ties of more than half a century ago.
The English and Spanish champions first played in Bilbao. The January weather in Northern Spain can be harsh and snow rendered Bilbao airport treacherous and deserted when United arrived.
"My impression of Spain being sun and sand were based on holiday posters at railway stations, so I was surprised that it was freezing," recalled the defender Bill Foulkes.
"It was our first season in Europe and we were unbeaten until Bilbao gave us a real going over in front of 60,000. The pitch wasn't good, it was covered in slush and mud and it got worst as the game continued."
Quicker and fitter, the Basques hit United with three goals in the first half, then came again with two more after Tommy Taylor and Dennis Viollet had led a United comeback in the second half. Billy Whelan gave the English side some hope when he made it 5-3, but United were outclassed.
"Bilbao had the best centre half I'd ever seen, Jesus Garay," said Foulkes. "He was so good that he kept Tommy Taylor quiet for most of the game and I'd never seen anybody do that."
It was United's first European defeat, but Matt Busby, the manager, was confident he could overturn the deficit in the second leg.
"Matt instilled in us a confidence that made us think we could still handle them back in Manchester," said Foulkes.
"But first we had to get back. There had been a snowstorm and players had to brush the wings clean of snow so that we could take off."
That memory was accompanied by disturbingly prophetic pictures of the United players clearing snow off the plane for the return flight to Manchester, via a bumpy refuelling stop in the Channel Islands.
The second leg was on February 6, 1957, exactly a year before the Munich air disaster.
Old Trafford had no floodlights so the game was held at Maine Road, Manchester City's former ground. Seventy thousand packed the banks of terracing in the stadium, the atmosphere superb, the play frenzied. United needed an early goal but it didn't come.
"We'd grown accustomed to United winning but this was different territory," said Wilf Breen, a fan who was there.
No wonder the visitors were determined to hang on.
"We heard that the Bilbao players had been on £200 [Dh1,156] a man to [about 10 times their weekly wage] to win," said Sir Bobby Charlton.
United looked doomed, especially as the Basques were playing with an extra defender. The consensus that English football was somehow superior to anything Continental Europe could offer had been shattered, but Viollet put United ahead just before half time. In the 70th minute Taylor made it 2-0 to level the scores 5-5 on aggregate.
"Noise decibels can be confusing and memory can overstate past exploits, but this was something out of the ordinary," said Breen.
Five minutes from time, one of United's greatest victories was confirmed when Johnny Berry scored from a Taylor cross. United won 6-5, with Piru Gainza, the Athletic captain, acknowledging that: "They play with such passion we were simply overwhelmed."
United would face the Real Madrid of Di Stefano and Puskas in the semi-finals. The English Football Association had opposed any English team entering European competition, but the result had vindicated Busby's decision to take his side into Europe and FA charges were dropped against United.
"Busby had declared that this was the future of the game and this was the hardest evidence that he was right," Charlton said.
"United against Bilbao had produced the best of football, some brilliant skill and a razor edge of competition."
United lost 3-5 on aggregate to Real. And then they tragically lost most of the Busby Babes a year later on a Munich airfield.
UAE TV: Man United v Athletic Bilbao, midnight, Al Jazeera Sport +4