United took the lead shortly after half time when Sergio Ramos bundled the ball into his own net, but things took a turn for the worse for the hosts when Nani was shown a red card for a challenge on Alvaro Arbeloa.
Here, Sports Mole takes an in-depth look at an eventful and controversial night at Old Trafford.
On target 11
On target 12
Was the result fair?
No. United were the better team until the red card and Madrid looked short of ideas when going forward. The hosts had two great chances in the first half and, although their goal had a big element of luck about it, they deserved to be in the lead. Madrid were on top in the period between the red card and the second goal, after which United reassumed control.
Man Utd's performance
It all looked to be going so well. Their first-half performance had everything but a goal, and they had chances to rectify that. Their defence kept Ronaldo very quiet and they were undoubtedly on top. Even after the sending-off, they rallied and put in a spirited performance, but ultimately the odds were just too great for United.
Real Madrid's performance
Jose Mourinho's men didn't have the best of games - as he admitted after the match - but I'm sure he won't care one bit. They were outplayed in the first half and needed the red card to gain control of the match. They struck twice in quick succession before sitting back and soaking up United's attacks while looking to counter-attack whenever the opportunity arose. They did this well, but it may have been a very different story if it had stayed 11 vs. 11.
Sports Mole's man of the match
Diego Lopez: The Madrid keeper made a string of very important saves to keep his side in the tie. He saved twice from Danny Welbeck in the first half and also pulled off good stops from the likes of Robin van Persie, Michael Carrick and Nemanja Vidic as United looked for a route back into the match.
There are a number of contenders for this one, but the one that had the biggest impact on the match was the red card. Nani only had eyes for the ball and did not see Arbeloa until it was too late. By the book, the referee will be able to justify his decision, but Nani was simply trying to control the ball and did not deserve to be sent off.
Poor. Cuneyt Cakir had a solid opening half but got a number of big decisions wrong in the second 45. The red card was extremely harsh, and he also missed a handball by Rafael on the line as well as a clear penalty for United. He will not be on Sir Alex Ferguson's Christmas card list.
Man Utd: United have another big test on Sunday as they host Chelsea in the FA Cup.
Real Madrid: Madrid's next match also comes on Sunday, when they will face struggling Celta Vigo in La Liga.