Embattled manager Jose Mourinho rang the changes to revive their ailing campaign. Out went Alexis Sanchez and veteran Antonio Valencia -aiming to chase down three points.
But tragedy struck inside seven minutes after a throw-in gone wrong found its way to Kenedy who finished incisively well after cutting inside Ashley Young from a through ball by Ayoze Perez.
It was two soon after as Yoshinori Muto turned from inside the box from another throw-in to beat David De Gea hands down two minutes later.
Newcastle as a consequence became the first side ever in the league’s history to score a double in the opening 10 minutes against Manchester at Old Trafford.
The backlash from the home crowd forced Mourinho to an early change and Eric Bailly went out for Marcus Rashford on 19 minutes.
Newcastle continued pressing forward than resting on their laurels after Perez managed to turn from just inside the box but shot straight at De Gea.
The Red Devils orchestrated undoubtedly their best chance towards the half and hour mark when Romelu Lukaku crossed for Rashford at the far post but the latter failed to capitalise, heading wide.
In the 34th minute, the Magpies closed in on a third for the halftime break but Jamell Lascelles was foiled by De Gea following a corner.
Later, the Toon were unlucky not to earn a penalty after Jonjo Shelvy’s free-kick from out wide was adjudged to have made slight contact with the arm of Young once the wall got up to try and defend.
Earlier in the second half, Paul Pogba’s low shot nearly crept in the bottom corner but Martin Dubravka pushed it back to play only for Nemanja Matic to balloon the rebound.
It was no surprise to see the Red side making all the attacking, but still struggled to get the breakthrough in the process.
Mourinho made his final change. In came high-profile arrival Sanchez for Rashford. The Red Devils pulled one back on 70 minutes when Mata’s medium-high free-kick found the low corner.
A string of saves from Dubravka from first Marouane Fellaini and then Chris Smalling frustrated the home side and their quest for an equaliser even further.
The equaliser was inevitable after Anthony Martial combined with Pogba to beat Dubravka at the near post on 75 minutes.
With time running out, both sides chased down the winner but lacked the cutting edge to cut each other open.
The comeback was completed a minute into added time as Sanchez rose high to head in the bottom corner for an amazing come back victory from the under-fire club.