But they needed to fight back after trailing to an early Peter Lovenkrands goal that was cancelled out by the break by Wayne Rooney before Dimitar Berbatov grabbed the all important winner.
Newcastle started brightly enough and got off to a dream start following a howler from Edwin van der Sar.
The giant Dutch keeper has been masterful this season but it was his blunder that gift-wrapped Lovenkrands a second Newcastle goal and first at St James' Park.
Lovenkrands started the move on the edge of his own area by finding Obafemi Martins who played in Jonas Gutierrez.
The Argentine international then cut in from the left to hit a drive that the keeper spilled and Lovenkrands rammed in the rebound.
Martins then worked himself into an excellent position soon afterwards before he was cynically brought down by Nemanja Vidic who was yellow carded.
It was all square after 20 minutes with Rooney spraying the ball wide to John O'Shea, who powered forward to pick out the England striker and he drove over skipper Steve Harper, who should have done a lot better.
The game erupted on the stroke of half-time when Steven Taylor caught Cristiano Ronaldo with his fist and, in the fury that followed, he was cautioned as was Rio Ferdinand for protesting that the Newcastle defender should have been red carded.
The Ronaldo and Steven Taylor confrontation continued down the tunnel at the break with Ferdinand also involved.
Again Newcastle showed early qualities in the second half before pressing the self-destruct button on 56 minutes.
A deep ball into the box produced a woeful attempt from Ryan Taylor to play the ball back to Harper and Ji-Sung Park nipped in to tee up Berbatov for a simple goal.
Newcastle's last win over the Old Trafford side was when they edged a seven goal thriller in the 2001/02 season and since then United have won 12 of the last 15 encounters.
Berbatov and then Rooney both had chances to increase the United lead, while at the other end van der Sar pulled off a good save to deny Martins an equaliser and secure another win for Sir Alex Ferguson's side.