Manchester United will face Real Madrid in the last-16 of the Champions League, Arsenal will travel to Bayern, while Celtic have been handed a tie against Italian champions Juventus.
The tie of the round sees Cristiano Ronaldo return to his old club for the first time since leaving for £80 million in 2009 - while it will also pit Jose Mourinho against Sir Alex Ferguson, with many considering the Portuguese to be the natural successor to Ferguson at Old Trafford.
Ronaldo scored 118 goals in 292 appearances for United, but it was another Ronaldo - the Brazilian striker - who took the honours when the clubs last faced each other in 2003, scoring a hat-trick at Old Trafford as Real went through 6-5 on aggregate.
The clubs, who both have a rich history in the competition, first met in the European Cup in April 1957, when Real triumphed 5-3 in the semi-final.
United defender Rio Ferdinand immediately made it clear he was excited at the draw, tweeting: "Oh yes, Madrid!! What a great couple a games that'll be!! @Cristiano see u soon bro!!"
United's club secretary John Alexander hoped there was a lucky omen in the draw. He told Sky Sports News: "Out of several standout ties, I think this is the one. It's the tie that everyone wanted to see - but that nobody wanted to see, they wanted to save it for later in the competition.
"When you think about the traditions of these two clubs they have both been incredibly successful, but of course the past is history. One thing going in our favour is that our one victory over Real Madrid in this competition was in the year we won the final at Wembley [in 1968] so let's hope that is a lucky omen.''
Arsenal, meanwhile, will face last year's runners-up Bayern Munich for a place in the quarter-finals of the competition - while Celtic will face Italian champions Juventus, who helped knocked holders Chelsea out of the competition at the group stage.
Elsewhere in the draw, a glamour tie sees two European heavyweights, AC Milan and Barcelona, go head-to-head for the right to reach the quarter-finals.
In a remarkable coincidence, all eight draws exactly matched those made during Wednesday's rehearsal - with Malaga facing Porto and Shakhtar Donetsk going up against Borussia Dortmund.
The two remaining matches see Galatasaray facing Schalke, while Paris St Germain have been drawn against Spanish side Valencia.