However, although down, the English champions are far from out of this season's competition.
Porto coach Jose Mourinho knows that and, ominously for him, so does United boss Alex Ferguson.
"The important thing is that we have a good chance of winning the second leg," said Ferguson after a bitter-sweet night in which he became the first man to coach a team in 100 Champions League matches but saw his side lose after taking an early lead.
"I think Porto recognise that themselves. It's difficult for opponents to win at Manchester on a European night. Our record there is outstanding, so hopefully we can produce our best form on the night."
Mourinho rightly enjoyed the moment but admitted his team failed to put the tie beyond United's reach after creating 21 goalscoring opportunities.
"We could have killed them off, we had the chances to score more goals," he said after Porto overcame the deficit of an early goal by United's South African midfielder Quinton Fortune to win with two goals from his own South African, Benni McCarthy.
He also played down any hint of a confrontation between himself and Ferguson after the final whistle, saying: "Not at all, sometimes there is a lot of emotion and sadness from a coach at the end of the match if his team has lost. I will shake his hand at Old Trafford."
He might not shake hands with Roy Keane though. The United skipper was sent off after 87 minutes after a linesman spotted him stepping on Porto goalkeeper Vitor Baia.
While Ferguson thought the keeper "made a meal" of the challenge, Mourinho said his goalkeeper stated afterwards that Keane definitely kicked him.
Either way the 11th dismissal of Keane's United career means that he will be suspended from the second leg.
UNITED UNBALANCED
United's problems run deeper than that, however.
The confidence and authority that David Beckham and a more youthful and mobile Keane brought to the team was missing for Ferguson's team.
With Beckham long gone to Real Madrid and Keane unable to roll back the years, United, seven points adrift in the English premier league, are going through a period of transition.
They are still a formidable force but Keane's sending off on Wednesday and Gary Neville's dismissal in an FA Cup match against Manchester City on February 14 hints at a sense of frustration creeping into the camp.
United looked unbalanced on Wednesday and created few scoring chances for either Ruud van Nistelrooy or Louis Saha, making his Champions League debut following his move from Fulham.
Without the injured Mikael Silvestre and the suspended Rio Ferdinand in defence, they allowed Porto far too much room coming forward.
Mourinho's plan of giving McCarthy and new Brazilian striker Carlos Alberto the freedom to roam in front of a midfield trio of Maniche Ribeiro, Deco Sousa and the influential Dmitri Alenichev caused United problems throughout.
The English champions are unlikely to have it any easier in the second leg.