Marseille could have no better incentive than to hear of Celtic's 5-1 downfall in Barcelona, and they duly recorded the victory that ushers them into the knockout stages with the Catalans.
Jordy Hiwula gave City some hope with a deserved equaliser just before the break, but a solid defensive display marshalled by skipper Sean Tse was undone near the end by Brice Bonelli.
It left the home side - supported by French World Cup winner Patrick Vieira in a sparse crowd - to lament a campaign that brought a wealth of experience but no points from the toughest of groups in which they finished as backmarkers.
Marseille, fielding just two of the players who won 3-0 in France last month, certainly didn't start like a team in a desperate race with Celtic to qualify for a shot at the main prize.
It was City who looked the more likely to score, but when Adam Drury fed the overlapping Tom Smith, the full-back's searching low cross found no takers and was hammered clear.
The French were by no means comfortable at the back, and goalkeeper Julien Fabri found himself forced to handle outside the box, earning an inevitable yellow card for his indiscretion.
But the keeper was more than a match for Joan Roman's driven free free kick, and gradually Marseille began to put together the passes to trouble the Blues' back four.
Santiago wasted one free kick, drifting the ball aimlessly beyond Tom Halsall's far post, but the visitors were getting the measure of their hosts and went ahead after 34 minutes.
This time Santiago's free kick, from a more central position, was driven with such force that Halsall could only parry into the air, allowing the onrushing Thomas Savino to head home.
Santiago was really in the mood now, and chanced his arm with a fabulous curling shot that barely cleared the angle as Halsall looked on
But with Hiwula around, there is always the chance of a goal, and it came after 42 minutes when the in-form striker beat Fabri all ends up with a cracking header into the roof of the net.
News of Celtic's demise in Catalonia in the earlier kick-off should have given Marseille fresh incentive, yet it City who looked threatening, even if they created little danger to Fabri's goal.
That changed after 74 minutes when Dennis Suarez danced his way through the French defence then, with only Fabri to beat, slammed his shot past the post when it seemed easier to score.
The young Blues were to rue that miss. Bonelli appeared to let them off the hook by missing a 79th-minute spot kick when Courtney Meppen-Walters handled, but he took the ball round Halsall to score the winner a minute later.