It will also pit Jose Mourinho against Sir Alex Ferguson in the most mouthwatering tie of the first knock-out round of Europe's top club competition.
The only other English side Arsenal will face last season's beaten finalists Bayern Munich while Celtic will take on Italian champions Juventus as they look for a place in the quarter-finals.
In the other matches, Barcelona will take on AC Milan, German champions Borussia Dortmund face Shakhtar Donetsk, Valencia play Paris St Germain, Porto encounter Spanish side Malaga and Galatasaray will come up against Schalke.
United have a slight advantage over Real in that as group winners they will get to play the second leg at home.
Arsenal and Celtic, who were group runners-up, will both play their second legs away.
Source: PA
Source: PA