Match ends, Tottenham Hotspur 1, Newcastle United 2.
Substitute Ayoze Perez scored three minutes into stoppage time as Newcastle came from behind to beat Tottenham and move out of the relegation zone.
Magpies keeper Rob Elliot frustrated Spurs with two fine saves to deny Erik Lamela before Eric Dier struck.
Dier was unmarked when he glanced home Christian Eriksen's corner.
Newcastle levelled when substitute Aleksandar Mitrovic tapped home after a scramble inside the six-yard box before Perez struck deep into stoppage time.
Newcastle's third win in five games lifts them three places to 15th, Norwich City dropping into the relegation zone.
Tottenham, who would have climbed above Manchester United into fourth spot with victory, are now without a league win in three games.
Can Newcastle stay up?
Steve McClaren and his Newcastle players were facing another bad day when the Magpies defence forgot to mark Dier, who glanced home his third goal of the campaign six minutes before the interval.
Elliot had already made two excellent saves to keep out Lamela and the Newcastle keeper later denied Harry Kane.
Yet the visitors showed spirit and desire - ingredients missing for long spells of the season - to produce a victory that had appeared very unlikely.
They were rewarded for their persistence 16 minutes from time.
Mitrovic, who had only been on the pitch two minutes, bundled an equaliser after Toby Alderweireld and Hugo Lloris failed to clear Chancel Mbemba's header.
Perez sealed a dramatic finish when he sneaked inside Jan Vertonghen before striking the ball past Lloris at the near post.
Tottenham's lack of cutting edge costly
Tottenham's first defeat since the opening day of the season, coming off the back of a home Europa League game, will not trigger any alarms at White Hart Lane.
But boss Mauricio Pochettino will be concerned at his side's failure to kill off teams. Three times in their past five league games Spurs have taken the lead and not won.
The defending for both Newcastle's goals left a lot to be desired, but Spurs should have doubled their lead before Newcastle scored their first.
As well as Elliot performed for the visitors, Danny Rose and Kane were guilty of missing good chances.
Man of the match - Rob Elliot (Newcastle)
What the managers said
Tottenham manager Mauricio Pochettino: "Our first half was fantastic - we dominated the game. The second is not easy to explain.
"We made mistakes and we feel very disappointed now because we did not deserve to lose.
"But that is football and you need to compete over 95 minutes. Today was difficult."
Newcastle manager Steve McClaren: "It's answered the critics we have had over last four weeks and it was a great performance in the second half and a great result.
"That is what we are, a bedrock of discipline and hard work. We have talented players, and they know how to win, we just have to do it consistently.
"We haven't turned the corner yet - we need more performances like that. We have been inconsistent."
The stats you need to know
- Christian Eriksen now has six assists in the Premier League this season - only Gerard Deulofeu (7) and Mesut Ozil (13) have more
- Tottenham have scored 10 goals from set-pieces (including penalties) in the league this season, more than any other side
- Spurs missed the chance to record their longest unbeaten run (15 games) in the top flight since 1967
- Aleksandar Mitrovic became the first Newcastle player to register an assist and a goal in a Premier League away game since Sylvain Marveaux against Arsenal in December 2012
- Newcastle have won back-to-back Premier League games for the first time in over a year (November 2014)
- Tottenham lost a home game having led for the first time since October 2014 - that game was also a 2-1 defeat by Newcastle
Pochettino takes Spurs back to his former club Southampton on Saturday before they entertain Norwich City on 26 December.
Newcastle face a big home game against bottom club Aston Villa on Saturday then host Everton on 26 December.
- 3RoseBooked at 73mins
- 28CarrollBooked at 68minsSubstituted forSon Heung-Minat 69'minutes
- 11LamelaSubstituted forChadliat 86'minutes
- 7Son Heung-Min
- 8AnitaSubstituted forGouffranat 90+1'minutes
- 4ColbackBooked at 30mins
- 10de JongSubstituted forPérezat 63'minutesBooked at 80mins
- 9CisséSubstituted forMitrovicat 72'minutes
- Roger East
- Shots on Target
Second Half ends, Tottenham Hotspur 1, Newcastle United 2.
Goal! Tottenham Hotspur 1, Newcastle United 2. Ayoze Pérez (Newcastle United) right footed shot from a difficult angle on the right to the bottom left corner. Assisted by Aleksandar Mitrovic with a headed pass.
Substitution, Newcastle United. Yoan Gouffran replaces Vurnon Anita.
Attempt saved. Dele Alli (Tottenham Hotspur) right footed shot from outside the box is saved in the centre of the goal. Assisted by Christian Eriksen.
Corner, Newcastle United. Conceded by Harry Kane.
Substitution, Tottenham Hotspur. Nacer Chadli replaces Erik Lamela.
Attempt missed. Son Heung-Min (Tottenham Hotspur) right footed shot from outside the box is too high. Assisted by Danny Rose.
Attempt blocked. Christian Eriksen (Tottenham Hotspur) right footed shot from outside the box is blocked. Assisted by Harry Kane.
Dele Alli (Tottenham Hotspur) wins a free kick in the defensive half.
Foul by Moussa Sissoko (Newcastle United).
Ayoze Pérez (Newcastle United) is shown the yellow card for a bad foul.
Jan Vertonghen (Tottenham Hotspur) wins a free kick in the defensive half.
Foul by Ayoze Pérez (Newcastle United).
Eric Dier (Tottenham Hotspur) wins a free kick in the defensive half.
Foul by Ayoze Pérez (Newcastle United).
Foul by Erik Lamela (Tottenham Hotspur).
Vurnon Anita (Newcastle United) wins a free kick in the defensive half.
Attempt missed. Son Heung-Min (Tottenham Hotspur) right footed shot from the right side of the six yard box misses to the right. Assisted by Erik Lamela with a cross following a corner.
Corner, Tottenham Hotspur. Conceded by Paul Dummett.