United were in charge throughout, and the margin of victory may have been greater had it not been for Mark Schwarzer.
Fulham recovered from the early setback and started to enjoy more and more possession without troubling United's defence.
The home side were actually the ones who looked more dangerous. A second penalty shout was turned away by the referee before Nani drilled the ball across the box to Rooney, but somehow his shot was saved on to the bar by Schwarzer.
As United grew in confidence, a second goal looked imminent. A great ball from Giggs put Nani through but the Portuguese failed to hit the target, before Rooney's tame shot from 25 yards was gathered by the goalkeeper.
Another good save from Schwarzer on the half-hour mark denied Rooney after a blistering counter-attack involving Giggs and Michael Carrick.
United were back on the attack as soon as the second half started. Nani dribbled past John Arne Riise before cutting the ball back, but again Rooney failed to find a gap through the bodies.
He wasn't to be denied for long though, a minute later, Anderson's through-ball found the England striker, who cut inside Hughes and smashed the ball past Schwarzer with his left foot.
Two minutes later it was 3-0. Rooney got to the by-line, and after being flicked on by Nani, his cross found Javier Hernandez, who volleyed the ball home.
United eased off after that, happy to play keep-ball and counter-attacking football.
That didn't stop them scoring though. Another Anderson through-ball found Hernandez who cut inside, before seeing his deflected shot escape Schwarzer.
With 15 minutes to go, United went to sleep at a corner and allowed Hughes to head home a consolation goal for the away side.
It could have been 5-1 a few minutes later when Rooney had the ball in the net again, but Clattenburg spotted a foul by Hernandez in the buildup.
United were happy with their work though, and saw the game out for a comfortable victory.