United were firm favourites to progress after Carlos Tevez's late equaliser in Lyon two weeks ago had secured a priceless away goal and the Red Devils eased into the hat for the last eight with few scares on the night.
The home side always looked in control with Ronaldo, Wayne Rooney, Nemanja Vidic, Anderson, Michael Carrick and Darren Fletcher all restored to the starting line-up following the weekend victory over Fulham.
United dominated possession, but failed to carve out many clear-cut openings during a tight opening in which the closest either side came to breaking the deadlock was a low drive from Ronaldo, which was blocked by Brazilian defender Cris.
Fletcher pulled a 25-yard shot wide of the mark, while at the other end Edwin Van der Sar parried a piledriver from Kim Kallstrom away from danger.
However, as has so often been the case this season, Ronaldo provided the game's decisive moment with a rare poacher's effort just before the interval.
Wes Brown's cutback was side-footed towards goal by Anderson and the ball dropped favourably for the Portuguese winger to take a couple of touches, before squeezing a left-foot shot from six yards inside the post.
United seemed content to play out time after that, but could have added a killer second goal during the latter stages of the second half.
Rooney just failed to pick out the unmarked Tevez with a 72nd minute cross, before wasting a glorious chances himself when he could only fire straight at Gregory Coupet after a dreadful back-pass from the disappointing Hatem Ben Arfa.
In between, the home side had a let-off when Lyon substitute Kader Keita came within a whisker of setting up extra-time when his low shot from the corner of the penalty area cannoned away off the foot of Van der Sar's upright.
But that would have been rough justice on United, who never seriously looked under threat during a comfortable European night at Old Trafford.