A second-half hat-trick from the impressive Sanli Tuncay handed the home side a comfortable victory, in a game that counted for very little.
In the night's other Group D clash French champions Lyon beat Sparta Prague 5-0 to clinch top spot and possibly an easier draw in the first knockout stage.
With qualification already secured Sir Alex Ferguson chose to leave many of his first choice players in Manchester and named an unfamiliar starting line-up captained by Phil Neville, with David Bellion as a lone striker.
The Turkish champions also had little to play for, as they were already guaranteed third spot and a UEFA Cup place, and the match's lack of importance shone through in a dismal first half.
The visitors created just one clear chance before the break but Bellion fired miserably wide.
Fenerbahce were very little better, with a long-range effort from Tuncay, a free-kick from Alex and a tame header from Nobre their only efforts on target – all gathered easily by Tim Howard.
The game sprang into life immediately after the break when Tuncay acrobatically volleyed Umit Ozat's cross in off the crossbar to put the hosts ahead.
They almost doubled their lead a minute later but Marco Aurelio hit a Balci Serkan cross wide of Howard's goal.
Kieran Richardson miscued when presented with United's best chance of the evening, before Fenerbahce doubled their lead in the 62nd minute.
Richardson conceded a free-kick on the right side of the box and Tuncay ghosted in unmarked to head home from Alex's delivery.
After the brief flurry of activity the match fizzled out again.
Cristiano Ronaldo finally managed to get United's first shot on target of the night after 73 minutes, but Rustu Recber gathered comfortably.
Howard produced a fine save to deny Tuncay his hat-trick, but the Fener playmaker was not to be denied.
Deep into stoppage-time Alex surged through the United defence before pulling the ball back for Tuncay to coolly place it beyond Howard.