Looking for the points to boost their European qualification hopes, Eddie Howe's side fell behind to Kobbie Mainoo's first half strike but Anthony Gordon - who had a penalty shout turned down before the break - turned in his 11th Premier League goal of the season to level matters after the restart.
It was a pulsating contest which Newcastle will feel they could have taken something from, but Amad Diallo's 57th-minute goal left Newcastle with work to do before Rasmus Højlund made sure of the points with a tody finish late on - though Lewis Hall did reduce the deficit in stoppage time with an excellent strike from distance.
Some early running from the visitors made it a lively start, with Alexander Isak flashing one well wide and Gordon being denied by a timely Sofyan Amrabat challenge in the box. A thumping intervention from Johnny Evans seconds later prevented Elliot Anderson from shooting but it set the tone for an absorbing encounter.
There were a few openings carved out by Erik ten Hag's men, most notably a Casemiro overhead kick that cleared the crossbar and a Diallo drive that was beaten away by former Red Devils loanee Martin Dúbravka, but aside from a Hall effort that tested Andre Onana the hosts were just about good value for their opener at the moment it arrived.
After Dúbravka got down well to repel Alejandro Garnacho at the end of a swift counter-attack, Manchester United took the lead when Diallo's delicate pass found an unmarked Mainoo in the box. The England youngster rolled home but it preceded a spell of pressure from Howe's side; when Dan Burn looked to have levelled from a back-post Kieran Trippier cross, Casemiro nodded the ball off the line, while Gordon saw a reasonable shout for a penalty waved away by referee Rob Jones after being felled in the box by a combination of Amrabat and Casemiro. Bruno Guimarães then headed a Trippier corner wide as the Magpies finished the first period well - save for an excellent challenge from Jacob Murphy, which denied Diallo in stoppage time.
Newcastle began well after the restart, with Guimarães' deflected shot held by Onana and Gordon's effort blocked by Casemiro before Anderson skewed one past the upright. They were rewarded for their endeavour just three minutes into the second half. Isak's through ball played in Murphy on the right, and his low whipped cross was perfect for Gordon, who turned home inside the six-yard box.
After Dúbravka turned away Bruno Fernandes' strike, Howe's side had a glorious chance to move in front. Aaron Wan-Bissaka surrendered possession and Gordon's speed created a two-on-one situation, with Isak up with him. He played in the Swedish frontman but the recovering Amrabat somehow got himself in the way of his shot, deflecting it up onto the crossbar.
But before the hour, they were undone by a set piece from Fernandes. Newcastle failed to clear the Red Devils captain's corner and Diallo was unforgiving, blasting first time beyond Dúbravka to restore the hosts' advantage. Diogo Dalot then forced a save from the Slovakian with a stinging strike from range.
Howe responded by making a triple substitution, introducing Joelinton, Fabian Schär and Miguel Almirón as he sought to halt some of their opponents' rhythm. They almost did just that when first, Sean Longstaff went one-on-one with Onana who kept his finish out, and then Joelinton climbed highest at the back post to force another stop from the former Inter Milan stopper, who got something on the Brazilian's header to divert it onto the bar.
With just under 20 minutes remaining, Newcastle went agonisingly close again. Gordon skipped past Casemiro in the box and his cross-shot only needed a touch but Almirón, flying in on the far side, was milimetres away from connecting with it; had he got anything on it, it would have been 2-2.
But in the 83rd minute, a third goal for ten Hag's men - against run of play - ended United's hopes of recovering. It came from another breakaway, led by Fernandes and substitute Marcus Rashford, and his fellow replacement Højlund finished it off with an angled low shot that found the bottom left-hand corner.
The Magpies did muster a consolation in stoppage time, though, thanks to Hall's superb curling long-ranger - but it wasn't enough to spark a late comeback on this miserable evening on the road for the Magpies.
