United opened their Barclays Premier Reserve League campaign with a 2-1 defeat against Arsenal but Darren Fletcher played the full 90 minutes.
The Scot made a successful return from a virus but Warren Joyce's team were beaten despite a well-taken goal from Mame Biram Diouf, who later went off injured.
Fletcher made a hefty early tackle and fed Paul Pogba with a fine pass as he settled in to his midfield role early on. Tomasz Kuszczak kept the scoresheet blank with saves from Kyle Ebecilio and Luke Freeman before United responded with a Diouf header wide and Danny Drinkwater's drive over the top following a neat interchange with Pogba.
A couple of injuries failed to disrupt the hosts and they went ahead on the half-hour mark when Fletcher's pass played Ezekiel Fryers into trouble and Freeman pounced to release Sanchez Watt. The former Leeds loanee wedged a clever finish over Kuszczak for the opener.
The Reds levelled with a well-worked goal as captain Darron Gibson spotted Pogba raiding down the right and his inviting delivery was met by Diouf's instant finish into the left-corner of the net. Vito Mannone then ensured the teams went in level at the break with a superb double stop to thwart Pogba and Diouf.
Diouf struck an Oliver Norwood pass straight at Mannone and the Italian keeper was out bravely to frustrate Pogba from a Gibson through ball. Diouf limped off due to injury and United lost their way a little with Kuszczak producing a fine stop when Watt latched onto a Fryers back-pass and then twice saving long-range efforts from Nico Yennaris.
The Pole had no chance, however, when Chuks Aneke made the most of a lucky deflection to force his way past Fletcher and Larnell Cole before shooting home courtesy of a huge deflection off Fryers.