Spurs started the better of the two sides as they attacked the Magpies straight from kickoff.
Gareth Bale gave the home side the lead after just four minutes, firing a 20-yard free kick just inside the near post to make it 1-0.
After nine minutes, Lewis Holtby almost made it 2-0 on his debut, but his effort from the edge of the area went just over the bar.
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Newcastle had a huge chance to draw level on 20 minutes, but Papiss Cisse could only direct his header wide from eight yards out.
The away side then grabbed a surprise equaliser on 24 minutes through Yoan Gouffran, whose shot from the edge of the area deflected off Michael Dawson and into the net.
Newcastle had the first opportunity of the second half on 52 minutes when a corner fell to Steven Taylor, who volleyed towards goal and saw his effort saved by Hugo Lloris.
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Bale grabbed a second goal to put Spurs back in front on 78 minutes, pouncing on Fabricio Collocini's hesitation to get himself in on goal and sliding the ball past Tim Krul from a narrow angle.
Steven Caulker should have made it three for Spurs on 82 minutes after Krul completely missed the ball, leaving the defender with a simple header to secure the points. However, the 21-year-old mistimed his effort and put it wide of the post.
Bale almost grabbed a hat-trick after 87 minutes when he skipped past two players before lashing the ball towards goal from 25 yards, but Krul was equal to the shot and tipped it over.
Shola Ameobi almost scored a dramatic equaliser for Newcastle in injury time, but a fine save from Lloris made sure the points went to Spurs.