Sir Alex Ferguson's men were handed a flying start as the Magpies' makeshift defence crumbled horrifically on two occasions inside the opening 16 minutes to allow first Jonny Evans and then Patrice Evra to head home.
Alan Pardew's men rallied in determined fashion and might have been back in the game five minutes into the second half, but Demba Ba's header came back off the bar and Papiss Cisse's follow-up was clawed on to the post by keeper David de Gea with the home contingent claiming the ball had crossed the line.
But Tom Cleverley's 71st-minute strike from long range ensured the visitors avenged their 3-0 defeat at St James' Park last season in fine style.
The bulk of a crowd of 52,203 trudged away knowing their team had contributed to its own downfall with the kind of calamitous defending which has plagued them for years, but had, until Sunday, become less common since their return to the top flight.
United dominated possession for long periods and had greater invention with Wayne Rooney, Robin van Persie and Danny Welbeck repeatedly stretching their hosts as Cheick Tiote and Yohan Cabaye struggled to exercise any real control in the middle of the park.
On a day when Newcastle found themselves linked with a sponsorship deal with loans company Wonga - it is understood the stadium naming rights are not involved - Pardew's players were handing out gifts for which there was no need for repayment.
Firstly, former Sunderland defender Evans left both Mike Williamson and Ba for dead to apply the finishing touch to Van Persie's right-wing delivery with eight minutes gone, and as many minutes later, Evra, hardly the most imposing of figures physically, was similarly unaccompanied as he reached Wayne Rooney's set-piece from the left with the same result.
Newcastle's defending was simply shambolic and while they could point to the absence of Tim Krul, Danny Simpson, Steven Taylor and Fabricio Coloccini, four certain starters in their first-choice back five, the men handed the marking jobs in their absence failed miserably in their tasks.
As the chaos unfolded, minds turned back to Arsenal's visit to Tyneside two seasons ago when Van Persie struck twice as the Gunners surged into a 4-0 lead by half-time, but only emerged with a point after being hit by a second-half blitz.
A repeat looked unlikely, but as Newcastle gradually climbed out of the hole they had dug for themselves, the mood inside the stadium began to change.
The movement of Rooney, Van Persie and Shinji Kagawa behind lone striker Welbeck had left the Magpies chasing shadows, and Pardew opted to switch Hatem Ben Arfa to the right to give his side a better shape and a greater attacking threat.
Gradually, his players worked their way into the game, Jonas Gutierrez dragging an 18th-minute shot just wide and Cabaye only just missing the target with a curling effort.
Ba turned a Cisse cross over the bar under pressure and Cisse headed wide from a Cabaye free-kick, but crucially, the Magpies failed to test keeper David de Gea.
A full-blooded 45 minutes saw five men booked by referee Howard Webb - Tiote and Gutierrez for Newcastle and Kagawa, Rio Ferdinand and Van Persie for United - and there was little sign of the tempo abating after the break.
Indeed, Newcastle thought they were back in it within five minutes of the restart when Ba got to Shane Ferguson's cross ahead of De Gea, but saw his effort come back off the bar.
Strike-partner Cisse headed the rebound towards goal, where the keeper managed to divert it on to the post with the striker insisting the ball had already crossed the line, but to no avail.
Ba headed wide from another Cabaye cross, but United continued to threaten on the counter and might have extended their lead when Welbeck held off Davide Santon and laid the ball off for Cleverley, but the midfielder skied his 57th-minute effort.
Keeper Steve Harper had to get down well to keep out Rooney's skidding left-foot effort three minutes later with the visitors pressing once again.
The home side kept plugging away with Hatem Ben Arfa dragging a well-struck left-foot shot marginally wide, but the game was over 19 minutes from time when Cleverley accepted Rooney's lay-off on the left wing and curled the ball right-footed across Harper and into the top corner.