Martin Jol made one change to his starting line-up with Aaron Lennon coming into the side. Hossam Ghaly returned and was named among the substitutes but after featuring in Tottenham's previous six games, there was no place for Danny Murphy.
Lennon and Defoe, were causing havoc with their pace in the early stages, the latter only narrowly losing out in a one-on-one situation with Shay Given. He was then at full-stretch to deny Lennon, and a dipping drive from Defoe flashed just wide. Tom Huddlestone tried the same thing and after a slight deflection saw his effort go wide as well.
Spurs dominated proceedings and went in front twice. Unfortunately, possession and clear chances that weren't converted came back to haunt the home side.
Given was beaten by Jermain Defoe and Dimitar Berbatov but the Newcastle stopper kept his side in the contest as the visitors came back as many times, against the run of play.
There was worse to follow when Nicky Butt stormed into the area and shot across Paul Robinson and into the net. Substitute Robbie Keane came very close before Defoe struck the crossbar. Hossam Ghaly and Berbatov so nearly combined to rescue a point, but it wasn't to be.
Martin Jol: "We didn't play badly, there was only one team that deserved to win, but it didn't work that way today. In fact, I felt we possibly played our best game this year.
We were stronger than Newcastle but we let ourselves down. We had a good team out - Aaron Lennon gave us that sparkle, Steed Malbranque, Dimitar Berbatov, I thought Jermain Defoe had his best game for Spurs since I've been here. We had all those ingredients and still lost. That was about us, not Newcastle. We also gave the lead away at Reading.
"I was very pleased in the first 20 minutes. Six or seven players went ahead of the ball, and didn't leave cover for the defence. Up front Malbranque, Lennon, Defoe could have scored three, Berbatov could have scored two, even Robbie Keane and Hossam Ghaly could have scored when they came on.
Michael Dawson: "It was a real sickener, a disappointing afternoon and I went home feeling down because it was a match we should have won, we didn't and we were all gutted about it.
"Losing a game that we played as well as we did in, was perhaps even harder to take than getting beaten comfortably."
Paul Robinson: "With the amount of chances we created we should have won the game. It was also disappointing to concede three goals at home.
"It was disappointing because we had the chances, but didn't take them."
Steed Malbranque: "The goalkeeper was very good and made some terrific saves, which was unlucky for me and the team. We were very disappointed after the game because we created a lot of chances. When they equalised it was not the same game afterwards.