Champions League - United through to quarters
Javier Hernandez put United ahead early on and despite several scares at the back the Mexican netted a second with 15 minutes remaining to put the home side firmly in the box seat.
But a Wes Brown own-goal on 82 minutes meant stress levels inside the ground remained high with the tie still on a knife edge during an anxious finale.
Yet the French champions were unable to seriously test their hosts again and United held out to progress to their fifth successive last-eight appearance in the competition.
Hernandez broke the deadlock with a simple fifth-minute tap-in after Wayne Rooney had started the move and then delivered the killer pass across the face of goal.
The strike followed a bright opening by United, who knew that victory on the night would see them progress to the quarter-finals after the first leg at the Stade Velodrrome had ended goalless.
But even a goal to the good, the tie was delicately balanced and an away Marseille goal would have turned the tie completely on its head.
That knowledge appeared to play on the minds of United's back line, which was missing the influential Nemanja Vidic after the Serb failed a fitness test on the calf strain he picked up at the weekend.
As such, Alex Ferguson was forced into fielding Brown and Chris Smalling in the centre of defence - the same pairing that played in the 3-1 defeat at Liverpool in the Premier League a week and a half previously.
And during the opening period, the makeshift back line did little to suggest United were going to maintain their excellent defensive record in this competition, which had seen them concede just once in seven previous games heading into this one.
Soon after Nani had opened the scoring, Smalling nearly got caught out as an innovative flick-on from Andre Ayew looped over the defender's head and into the path of Andre-Pierre Gignac. Only an abject finish from the France international kept United's clean sheet intact.
Souleymane Diawara was then allowed to meet a corner unchallenged but, again, United were saved by another atrocious finish, this time as Diawara conspired to head wide.
And on 42 minutes, Smalling's attempted clearance only found Loic Remy, who blazed a vicious first-time effort over the bar.
Yet United survived those scares and were actually the better side during the opening period, bossing possession and only lacking the nous to unlock the visitors' defence for a second time.
The second half was a different story as Marseille, forced to attack more and with United sitting back a little, began to enjoy more of the ball.
Benoit Cheyrou brought Edwin van der Sar into action on 74 minutes as the pressure on United's goal mounted but the hosts relieved the pressure as Hernandez hit on the break in virtually a carbon copy of his first goal.
The goal should have put the tie to bed, but Marseille extended their interest in the match when Gabriel Heinze - booed on his return to Old Trafford - attacked a corner and Brown bundled the ball into his own net.
Yet Didier Deschamps's side failed to take inspiration from the goal and what should have been a grandstand finish saw the French side fail to fashion any more chances.
The result sees United maintain their impeccable record against French opposition at Old Trafford - they have never lost to a side from across the Channel at home - and means they join Internazionale, Tottenham, Barcelona, Schalke and Shakhtar Donetsk in Friday's draw. Chelsea's fate will be decided on Wednesday when they meet FC Copenhagen, while Real Madrid play Lyon.