Chelsea boss Jose Mourinho was looking for a first ever League win at Newcastle but Papiss Cisse came off the bench to put the hosts 2-0 up.
The Magpies then had Steven Taylor sent off and Didier Drogba pulled a goal back for Chelsea but the hosts held on to secure a famous win.
Chelsea were comfortably the better side for the first half-hour and Willian twice put shots from the edge of the area just wide of Rob Elliot’s post, while Gary Cahill headed over from a Cesc Fabregas corner.
However, the hosts eventually roused themselves and almost took the lead when Ayoze Perez played in Jack Colback with a delightful little reverse pass, only for Thibaut Courtois to charge off his line and pull off a fine save.
But the visitors finished the half in the ascendancy and Oscar was not far wide with an acrobatic overhead kick just before half-time.
Newcastle goalkeeper Elliot picked up an injury when making a clearance just before the interval and had to be replaced by Jak Alnwick.
And the promising youngster was soon called into action, punching a Fabregas free-kick clear as Chelsea made a lively start to the second period.
Newcastle boss Alan Pardew decided a further change was necessary and his decision to bring Cisse on for Remy Cabella paid a swift dividend.
Moussa Sissoko made inroads down the left before setting up Sammy Ameobi for a low cross which Cahill failed to cut out at the near post, allowing Cisse (57) to turn the ball into the net from close range.
Sissoko then headed over the bar after the ball had bounced around following a corner, and Mourinho decided his side needed a revamp.
Andre Schurrle came on, and swiftly tested Alnwick with a low effort from 30 yards out, and he was soon followed off the bench by Drogba and Filipe Luis.
Chelsea began to dominate possession but Newcastle defended valiantly, led by captain Fabricio Coloccini, who brilliantly blocked a Diego Costa shot.
And Eden Hazard was then unlucky to see a shot come back off the post after he had been picked out in the box by Branislav Ivanovic.
But Newcastle then stunned the leaders by doubling their lead with a breakaway goal.
The hosts worked it neatly in the middle of the park, allowing Colback to play Sissoko in on goal and, although the midfielder got his legs in a mess and seemed to have squandered the chance, he poked the ball across to Cisse (78), who calmly fired into the empty net.
Chelsea were on the ropes but they got a lifeline when Taylor picked up his second yellow card of the match for a lunge on Schurrle 30 yards out.
And there was even greater encouragement for the visitors when Fabregas chipped the subsequent free-kick into the goal mouth and Drogba (83) got there before Alnwick to nod Chelsea right back into contention.
With seven minutes left, plus ample injury-time, Chelsea laid siege to the Newcastle goal and Alnwick produced a great save to tip a Costa shot over the bar.
The Newcastle goalkeeper then kept out a raking Luis drive from distance but there were more scares to come in six minutes of injury-time.
However, Ivanovic shot wide and Drogba glanced a header the wrong side of the post from Chelsea’s point of view, as Newcastle hung on to triumph after a tumultuous second-half which opened up the Premier League title race.