United had to come from behind to get off to a winning start in the Barclays Under-21 Premier League Elite Group.
Warren Joyce's side have been frustrated by the bad weather but were finally in action for the first time in 2013 down at Southampton.
A late switch of venue to Staplewood Training Ground led to the fixture being played behind-closed-doors and the Reds were rusty in the opening stages, falling behind to Lloyd Isgrove's header from an Omar Rowe cross.
Sam Johnstone's denied Isgrove on a couple of occasions with smart saves while Jesse Lingard was unlucky with a spectacular volley that flew off target.
United still trailed with 20 minutes left but Tom Lawrence levelled matters by capitalising on a mistake by Cody Cropper to lift the ball into an empty net. Cropper's day went from bad to worse when he handled whilst dispossessing Ryan Tunnicliffe outside of his box.
The visitors took full advantage with Adnan Januzaj bagging his first Under-21 goal from the free-kick with only five minutes remaining and there was still time for Marnick Vermijl to wrap things up from close range after substitute keeper Will Britt could only parry another Januzaj set-piece.
After drawing both fixtures with Southampton at this level earlier in the season, this was a tremendous, if belated, start to the new phase.
United: Johnstone; Vermijl, Veseli, Fornasier, McGinty; Cole (Blackett 90), Brown, Tunnicliffe, Lingard, Powell (Lawrence 46); Cofie (Januzaj 46). Subs not used: Gollini, Ekangamene.