Eddie Howe's side were the better team throughout and deservedly secured the three points thanks to second half efforts from Joe Willock and substitute Callum Wilson at a roaring St. James' Park.
Willock's opener after a patient move from the Magpies and Wilson's late header sealed United's first win over the Red Devils since 2019, gaining revenge for February's Carabao Cup final defeat to Erik ten Hag's men and lifting themselves above their opponents and into third place in the Premier League table.
The hosts, unchanged from the 2-1 win at Nottingham Forest before the international break, dominated the entirety of the first half and only a combination of David De Gea's interventions and their own profligacy prevented them from holding a half time lead. Sean Longstaff threatened first, seeing his effort from Alexander Isak's knockdown blocked before a brief foray forward from the visitors. Scott McTominay's crunching tackle on Bruno Guimarães went unpunished and seconds later Wout Weghorst had fired into the sidenetting, but it proved to be only a fleeting moment of pressure from the Red Devils.
Goalkeeper De Gea had much more to do early on than his opposite number Nick Pope. The Spaniard produced a fine double save to deny first Isak, who headed goalwards from close range, before somehow keeping out Willock's volleyed follow-up as the Magpies turned the screw in front of a vocal crowd.
Allan Saint-Maximin grew in influence as the half went on, seeing a shot held by De Gea and crossing for Longstaff to nod just wide. Longstaff then took aim from the edge of the box and saw his swerving drive flash just past the upright, with most of those in black and white preparing to see the net bulge as it made its way towards to top left-hand corner.
United's customary intensity was proving difficult for Erik ten Hag's men. Another burst, led by Isak and then Saint-Maximin, led to Willock blazing over from around 12 yards out in what was Newcastle's last opportunity of the first 45, but the second period's opening exchanges were a little cagier. Pope was finally called into action, comfortably holding a tame strike from Antony, while Fabian Schär - urged on by the Magpies faithful - whipped one just past the post from 25 yards.
Just after ten Hag had introduced Jadon Sancho and Anthony Martial in a bid to capitalise on his side's improved start to the second half, Newcastle struck at the other end. It was a goal that owed much to persistence, with Saint-Maximin heavily involved as he looked to force his way through a crowd of bodies on the edge of the area. Eventually the ball was played out wide and then to Guimarães in the box, and the Brazilian lifted a cross towards Saint-Maximin at the back post. The Frenchman did well to direct his header back across goal and Willock was there, arriving just in time to turn it home in front of the Gallowgate End.
The Red Devils looked to respond, with Marcel Sabitzer stumbling over one chance to get a clean shot away, but the game felt like Newcastle's to lose. They went agonisingly close soon after when substitute Joelinton's header, from point-blank range, was superbly diverted onto the crossbar by De Gea, with Schär's brave attempt to nod the rebound home seeing him denied by the post.
There were some brief glimmers of hope for the visitors - Martial saw his effort deflected wide and fellow replacement Victor Lindelof glanced a corner over the bar - but with just a few minutes left, United sealed the win with an excellent, simple second goal. Longstaff won a free kick down by the corner flag and Trippier sent it into the six yard box, where Wilson - who had been sent on in place of Isak - climbed highest to nod it home via the woodwork and round off a superb afternoon for Howe and his charges.
