He drifted inside his marker, Adrian Mariappa, before drilling a right-foot shot high into the roof of the net from the edge of the area, leaving Richard Lee grasping at thin air.
Four minutes later Lee was off his line quickly to prevent Rooney from reaching Alan Smith's low ball into the box from the right.
However, the Hornets were level with 26 minutes played, just after Edwin Van der Sar had received lengthy treatment for a head injury.
United failed to deal with a long throw, and when Tommy Smith played the ball back in, Hameur Bouazza's acrobatic left-foot volley was deflected high past Van der Sar into the corner of the net.
It was 2-1 to United within a couple of minutes though as Rooney skipped clear on the right flank and his cross-cum-shot took a touch off Lee and presented Cristiano Ronaldo with a close-range tap-in.
Five minutes before the interval Rio Ferdinand limped off with a groin problem, with Gabriel Heinze forced to move to centre-back to cover.
After the restart the game quietened down, before Van der Sar was stretched by a cross from the left by the impressive Bouazza.
Watford then looked like they might force their way back into the game, before they again left United with far too much time and space and Smith played the ball in from the right for Rooney to side-foot home from close range.
Twenty minutes from time the Hornets defence crumbled again, but, after Smith had beaten several challenges, Rooney scuffed his shot straight at Lee from 15 yards.
With eight minutes to play United made it 4-1 as Smith released substitute Kieran Richardson in the left channel and the former England midfielder raced clear before lifting a left-foot shot over the advancing Lee and into the far corner of the net.