The team controlled possession for long periods but were always chasing the game after going 1-0 down inside two minutes.
There was a touch of fortune about Federico Macheda's opener for United and the same player doubled the home side's lead from the penalty spot five minutes into the second half.
We continued to create chances and were eventually rewarded 10 minutes from time when Scott Wootton bundled over Harry Kane in the box and Ryan Mason drilled home from 12 yards.
That was the first goal United had conceded at reserve level in over 10 hours.
Cristian Ceballos and Kane then had chances to level in the final five minutes but it wasn't to be.
Kane and Mason were joined in the line-up by Adam Smith, Tom Carroll, Yago Falque, Andros Townsend and Jon Obika - all players with first team experience - for this Group Two encounter at Moss Lane.
There were familiar faces in the United team as well, led by Darren Fletcher and Jonny Evans and including new signings Nick Powell and Alexander Buttner.
United caught us cold inside two minutes as Ryan Tunnicliffe won possession centrally and released Macheda through on goal.
Jordan Archer was out quickly to block Macheda's effort but the ball cannoned back off a combination of Macheda and Caulker and flew into the empty net.
We gradually setted into the game and Yago Falque fired our first attempt at Anders Lindegaard in the 17th minute.
Our best spell followed between 25-40 minutes as Jon Obika's effort was blocked by Michael Keane, Kane headed just wide, Carroll curled over after Townsend's break, Falque's attempted chip floated wide and Kane couldn't get enough on his far-post header to seriously trouble Lindegaard.
United's best moments came on the break from the lively Joshua King, who zipped in a cross that just evaded Powell and then blasted over from 12 yards from Macheda's pass.
We were soon on the attack in the second half as Nathan Byrne fed Townsend, who clipped the ball over Lindegaard only for Buttner to clear off the line.
Milos Veljkovic joined the action four minutes into the half and seconds later, United went 2-0 up. Smith barged over Powell and Macheda sent Archer the wrong way from the penalty spot.
Undetered, we continued to keep hold of the ball and push forward.
Lindegaard made a fantastic double save to deny Obika and Kane in the 59th minute and seconds later, Obika's turn lost Wootton and Keane, but he fired into the side-netting.
Obika then tried the spectacular as Kane nodded back Byrne's deep cross, but Lindegaard was again tuned in to collect the striker's overhead kick. Obika and Kane combined once more after 72 minutes, Lindegaard this time saving comfortably down to his left.
King blasted over for United, who continued to look threatening on the counter without seriously testing Archer in the second half.
We were handed a route back into the game in the 80th minute when Wootton was penalised for a foul on Kane and Mason made no mistake from the spot.
There was time for two more chances. First, Kane's deep cross was headed out to substitute Ceballos, who went for precision from 18 yards but curled over. Then, in the final minute, Falque got to the right byline and crossed to the far post for Kane, whose header was blocked by Evans.
A draw would have been just reward, but there were plenty of positives on the night.
Manchester United (4-2-3-1): Lindegaard; Wootton, Evans, Keane, Buttner; Fletcher, Tunnicliffe; Brady (Lingard, 61), Powell, King (Thorpe, 84); Macheda (Cole, 65). Unused subs: Sutherland, Fornasier.
Spurs (4-2-3-1): Archer; Smith, Caulker (Stewart, 69), Hall (Veljkovic, 49), Byrne; Carroll, Mason; Falque, Kane, Townsend (Ceballos, 69); Obika. Unused sub: Vigouroux.