Virtuoso Ronaldo made the difference and notched a magnificent winner only after six minutes to earn Alex Ferguson's team a 3-2 aggregate victory.
Both teams drew 2-2 in the first leg at Old Trafford a week ago.
United will face their bitter rivals Arsenal, who defeated Villarreal 3-0 on the same day, in the next round.
The defending champions took a stranglehold on the game right after the kick-off.
Ronaldo cannoned an unstoppable shot from long range, taking advantage of an awkwardly-positioned Helton, to fire United ahead.
The Red Devils tightened their grip on the game after taking the lead, and kept looking for a second goal right away.
Porto got their act together almost after 20 minutes and sought to cancel out their opponents' slender lead, but couldn't carve out many clear-cut opportunities
Bruno Alves was the closest to bringing the score level in the first half, but his header on 40 minutes missed the target by inches.
United's Nemanja Vidic also wasted a golden chance to score when his effort from point-blank range went over the crossbar.
In the second half, the match's tempo pretty much remained the same, with the Premiership giants trying to ensure their superiority and Porto holding out hopes of qualifying for the next round.
The Portuguese side got the upper hand most of the time in the second term, while United's onslaught faded away.
Raul Meireles tried his luck on 48 minutes, but his neat shot went wide of the mark.
In the dying minutes, the home side exerted huge efforts to notch a precious equalizer, but a consistent United defense prevented them and kept the one-goal cushion.
In stoppage time, Ronaldo tried to put the icing on the cake and released a cunning low shot, but Helton parried it away.
Ronaldo's goal