Ronaldo settled an edgy tie which lacked any real quality shortly before half-time with a finish from close range.
Sir Alex Ferguson made wholesale changes with Ronaldo and Wayne Rooney among six changes to the side that beat Fulham 3-0 at Craven Cottage on Saturday.United dominated the opening period without really testing Gregory Coupet in the Lyon goal. Ronaldo had a couple free-kicks from long range which failed to get past the defensive wall and Darren Fletcher lashed wide from long range, but it was not until five minutes before half-time that United finally made their possession count.
Wes Brown's cutback from the by-line was cleared only as far as Anderson on the edge of the box. The Brazilian slid the ball into Ronaldo, who found the space on the edge of the six-yard box to lash the ball between Coupet and his near post to hand United the lead they deserved.
The French champions started the second half in more determined fashion but both keepers remained untroubled.
Nani's drive from the right hand corner off the penalty area was just off target in the 63rd minute before Rooney failed to find substitute Carlos Tevez when the home side broke ten minutes later.
Lyon came desperately close to an equaliser in the 73rd minute. Substitute Kader Keita combined well with Karim Benzema on the right before unleashing a low effort from the corner of the penalty area which struck the base of Edwin van der Sar's post with the Dutch keeper beaten.
Following their escape, United looked the more likely to add to their lead but wasted a number of opportunities to kill off the game because of sloppy final balls in the final third.
While United were far from their best, Ferguson will be relieved to progress into the last eight and can now focus on catching Premier League leaders Arsenal before the quarter-final first-leg at the start of April.