Goals from Casemiro and Isco secured a fully-deserved triumph for the Champions League holders, who have now won the trophy three times since 2014.
Romelu Lukaku halved the deficit on his competitive debut, but the Europa League winners looked well short of matching Madrid for much of the encounter in a hot and humid Philip II Arena, where drinks breaks were required.
United beat Madrid on penalties after a 1-1 draw in the International Champions Cup last month, but they were second best for the majority against Zinedine Zidane’s side, for whom Gareth Bale started and Cristiano Ronaldo made a late cameo appearance as a substitute.
Jose Mourinho handed first competitive starts to Lukaku, Nemanja Matic and Victor Lindelof, but it looked unlikely that he would celebrate a win over his old club from the moment Casemiro broke the deadlock after 24 minutes.
Isco’s superb second put Madrid in control in the second half and, although Lukaku gave United some hope of a comeback, Zidane’s side held firm to win their sixth trophy since the Frenchman took charge last January.