Martin Jol's side never recovered after conceding two early goals at St James' Park, with Kieron Dyer and Obafemi Martins giving Glenn Roeder's side the perfect start.
Danny Murphy pulled one back for Spurs, but the Londoners hopes of getting back in to the game faded after Scott Parker netted a third for the home side.
The afternoon hadn't started well for in-form Tottenham. Jol lost key man Jermain Defoe to a warm-up injury, the ten-goal striker limping off with a knee problem to be replaced by Murphy in the starting line-up.
And things did not get any better for Spurs when the game kicked off, with Jol's side conceding two soft goals inside the first seven minutes to give themselves a mountain to climb.
With just three minutes on the clock Nolberto Solano - playing at right-back in the absence of former Spurs defender Stephen Carr - cleared the ball upfield to Martins, who quickly sent makeshift striker Dyer away.
Visiting captain Ledley King stood off and Dyer picked his spot for his second goal of the season, tucking the ball neatly between Paul Robinson and his left-hand post.
Dyer's other goal had come against Spurs' north London rivals Arsenal in November's visit to the Emirates Stadium.
Four minutes later Roeder's buoyant side were 2-0 up. James Milner played the ball inside to Parker, who clipped to ball to Martins and he lost his marker Pascal Chimbonda to head home his ninth goal of the campaign.
United, however, didn't have it all their own way. By the 15th minute Tottenham had halved the deficit after a Murphy shot beat Shay Given, after taking a deflection off Steven Taylor.
Chimbonda broke down the right and crossed into the United box, and after Steed Malbranque failed to connect properly with an attempted overhead kick, Defoe's late replacement Murphy was there to direct the ball into the net off the chest of Taylor.
Newcastle almost restored their two-goal advantage five minutes later, but Dyer could not get out of the way of Nicky Butt's goalbound header.
Then - on the half-hour mark - Dyer powered into a crowded Spurs box from the right before firing a fierce shot from a tight angle which crashed against the nearside post. Their third goal, however wasn't long in coming.
And it came from Parker in front of the watching England coach Steve McClaren, with United's captain eventually heading the ball over the line after an almighty goalmouth scramble.
Milner's deep free-kick from the left was initially spilled by Robinson - whose afternoon was going from bad to worse - and Taylor was the first Newcastle player to react with the ball rebounding to Martins, whose effort was blocked.
The ball bounced for Parker to head home the sixth goal of his St James' Park career.
Two minutes into the second half Dimitar Berbatov flashed a shot narrowly wide as Tottenham attempted to find a way back into the game.
Shortly after the Berbatov chance, Given suffered what looked a hamstring injury, and Roeder sent Pavel Srnicek out to warm up. However, Given - careful to avoid eye contact with his bench - played on, with Peter Ramage taking his goal kicks.
And when Roeder made his first change, it wasn't Given coming off.
Instead, Antoine Sibierski replaced Emre in the 66th minute, while Jol brought on striker Mido for midfielder Didier Zokora as he looked to beef up his attack.
On-loan striker Giuseppe Rossi followed Sibierski on to the pitch in the 77th minute, with the appearance his last for Newcastle at St James' Park before he returns to Manchester United at the end of the month after a half-season spell on Tyneside.
And it was a memorable afternoon for fans favourite Srnicek in particular, who replaced Given in the 88th minute to make the first appearance of his second spell at the club.