After Manchester United had taken the lead through a Sergio Ramos own goal shortly after the break, Nani who had created the chance, was then sensationally sent off for a high boot into Alvaro Arbeloa's chest even though the United forward had his eye on the ball and caught the Madrid player unintentionally.
Madrid immediately increased the tempo and laid siege to the United goal and were rewarded on 65 minutes when substitute Luka Modric hit an effort from outside the area which found the back of the net via the inside of the post.
Four minutes later and the visitor's took the lead and went ahead on aggregate as a low drilled cross was met at the far post by Ronaldo to sidefoot home.
The noise inside Old Trafford was tremendous as the home side started to fight back with van Persie and Wayne Rooney having chances and the crowd claiming handball every time ball hit a Madrid defender in the penalty area or a home side player went down.
But even five minutes of added time was not enough for the Red Devils to salvage extra time as Madrid looked to catch them on the break.
And all this drama after a cagey opening 20 minutes even though the first chance arrived after only three minutes when Ronaldo, returning to Old Trafford for the first time in four years, hit a free kick into the wall. And it was the returning hero who also had a shot blocked from a dangerous position, but overall the first half chances belonged to the home side.
On 20 minutes Ryan Giggs, playing his 1000th game, fired in a corner which Nemanja Vidic headed against the post, then rebounded off Danny Welbeck into the grateful arms of the prone Spanish keeper Diego Lopez.
Welbeck and Robin van Persie then both had efforts charged down by the visitor's rearguard as United took the initiative.
Madrid had plenty of possession but created little, with Ronaldo in particular quiet.
Gonzalo Higuain did have the ball in the net for the Spanish team but it was correctly ruled out for a foul on van Persie.
How crucial was the woodwork which saved Madrid and the Turkish referee who controversially sent off Nani. Vidic was even denied in injury time as Lopez saved his bullet header.
Referee: Cuneyt Cakir (Turkey)
Venue: Old Trafford
Man Utd scorers: Ramos og 48
Real Madrid scorers: Modric 65, Ronaldo 69