An open, entertaining match in front of over 2,000 fans that included a power failure that wiped out the floodlights just before half-time was won by Ryan Tunnicliffe's strike in the 56th minute.
Already guaranteed a place in the play-offs, it was the first time we've failed to score and only our fifth loss in 24 matches in the Barclays U21 Premier League this season.
We have two matches remaining in the Elite Group - Arsenal at Barnet on Monday week, April 22 and then a trip to Southampton on April 29.
Both teams enjoyed spells of possession in United's first match at the home of Sale Sharks and Salford City Reds and we certainly bossed the first and last 15 minutes territorially without reward.
United goalkeeper Ben Amos was in fine form - as was Lawrence Vigouroux in the Spurs goal - and the closest we came to beating him was when Cristian Ceballos' free-kick struck the crossbar just before Tunnicliffe's winner.
Younes Kaboul started the second game of his return to action but departed early in the second half.
We started well, dominated play in the opening exchanges and had the only serious chance of the first 20 minutes when Ceballos nicked the ball from Michele Fornasier on the edge of the United box but Amos was out to make a fine block from the left angle.
United then clicked into gear and created three chances in as many minutes.
It started with Jesse Lingard aiming a shot inches wide from the edge of the box and then Adnan Januzaj clipped the top of the crossbar from 25 yards.
Vigouroux made a fine double save minutes later, first showing good reactions to palm away Tunnicliffe's deflected blaster and getting up quickly to turn around Lingard's follow up destined for the far corner.
The final chance of the half came via a trademark Kaboul piledriver free-kick from fully 30 yards on 35 minutes that Amos managed to shovel off his goal-line and wide.
Five minutes later and the floodlights went out due to a power failure in the Salford area. There was just enough natural light to complete the half and the floodlights were back on in time for the second half.
Kaboul was replaced by Jack Barthram three minutes after the re-start with Zeki Fryers moving into central defence.
Ceballos was inches away from opening the scoring on 54 minutes but after a fine save from Vigouroux to deny Januzaj, United went ahead on 56 minutes.
Lingard played into Tunnicliffe, who managed to wriggle away from Fryers and into the box centrally and just managed to poke the ball under the advancing Vigouroux.
Giancarlo Gallifuoco replaced Laste Dombaxe and immediately set-up a chance for Shaq Coulthirst. He floated a pass into the box and Coulthirst did well to hold off Fornasier and fashion an effort on goal, but Amos was there to block.
United then enjoyed another purple patch as Januzaj released Larnell Cole through the middle. One on one against Grant Hall, Cole rolled the ball left to Lingard but Vigouroux read it and was out to gather at Lingard's feet.
Cole then connected sweetly from 20 yards only to see his effort cannon back off the upright.
The game settled again after that and we re-asserted ourselves in terms of possession but this time, couldn't carve out a chance for an equaliser with United pressing us all over the pitch until the final whistle.
Spurs (4-3-3): Vigouroux; Fredericks, Kaboul (Barthram, 48), Hall, Fryers; Veljkovic, Dombaxe (Gallifuoco, 61), Bentaleb; McEvoy (Michael-Percil, 66), Coulthirst, Ceballos. Unused sub: Priestley.
Manchester United (4-3-3): Amos; Vermijl, Fornasier, Thorpe, James; Veseli (Blackett, 10; Lawrence, 84), Cole, Ekangameene; Tunnicliffe, Januzaj, Lingard. Unused subs: Sutherland, van Velzen, Hendrie.