Rooney double dumps out Milan
Rooney, who scored twice in the 3-2 San Siro win, was on target with a 13th-minute header that broke the hearts of the seven-times winners.
He added his second at the start of the second half and in a virtual exhibition match, Park Ji-sung after an hour and a late Darren Fletcher header completed the crushing victory.
"We got the break with the early goal in the second half and after that we played very well. When we play at that tempo we are difficult to play against. With the team I've got it dosn't matter who we play next," said United manager Alex Ferguson.
Milan, without injured centre back Alessandro Nesta, striker Alexandre Pato and midfielder Luca Antonini looked off the pace from the start but few could have predicted their total capitulation.
SERIE AAAARGH!: Humiliated Milan can't even save face
Rooney shot wide after three minutes and even fullback Gary Neville was allowed to let fly just over the bar with his left foot soon after.
Milan should have scored from their first real attack though as an Andrea Pirlo free kick reached Ronaldinho but the Brazilian's header went just wide after eight minutes.
If Klaas-Jan Huntelaar had managed to control Thiago Silva's through ball with the goal gaping things might have turned out differently.
With Daniele Bonera forced to operate at centre back Rooney was wandering free and when Neville found him on the penalty spot there was never any doubt that he would thunder his header beyond Christian Abbiati.
That left Milan needing three goals to progress and it appeared that nobody in their lineup had the confidence to find them.
Within a minute of the restart they needed four as more slack defending allowed Nani to charge forward down the left. He then sent in an inviting low cross with the outside of his right boot and Rooney made sure he reached it first to score his 30th club goal of the season.
Paul Scholes sent Park through to slide in the third as Milan just about went through the motions.
The introduction of David Beckham as a 65th-minute replacement for Ignazio Abate raised the biggest cheer of the night as the midfielder, who left United for Real Madrid in 2003, was given a standing ovation and even tested Edwin van der Sar with a sharp shot.
With not much of a contest to keep them occupied United's fans spent most of the last 20 minutes chanting anti-Glazer songs and displaying their green and gold protest scarves against the American owners of the club - Beckham left the pitch wearing one at full time.
They were brought back to the action two minutes from time when Fletcher stretched well at the far post to head home the fourth goal and complete Milan's humiliation.
With Arsenal moving though against Porto on Tuesday, Chelsea can make it a hat-trick of English sides into the last eight if they can turn round their 2-1 deficit against Inter Milan at Stamford Bridge next week.