Spurs led until the 57th minute at Old Trafford but a controversial penalty allowed United back in and they ran riot with two goals each for Cristiano Ronaldo [ Images ] and an inspired Wayne Rooney [ Images ] and one by Dimitar Berbatov [ Images ].
The win gave leaders United 77 points, three ahead of second-placed Liverpool who have played a game more.
"Carlos Tevez [ Images ] was responsible for that energy we got. Once we got the first goal it gave us a fantastic impetus and then we were magnificent," United manager Alex Ferguson [ Images ] told Setanta Sports after bringing the Argentina striker on at halftime.
"We were too casual, had no speed in the first half, nothing like the tempo we wanted to play at and we deserved to be down. I think we were a bit fortunate (with the penalty) but once we got that goal we were electric."
Spurs have not won at Old Trafford for 20 years but looked well placed at halftime.
Ragged defending by Rio Ferdinand [ Images ] allowed Vedran Corluka's cross to reach Darren Bent who scored after 29 minutes.
An Aaron Lennon cross was then controlled nicely by Luka Modric as he banged in the second three minutes later.
Tevez added some zest to United in the second half but they needed a lucky break to start the comeback.
Goalkeeper Heurelho Gomes [ Images ] dived at the feet of Michael Carrick [ Images ] and seemed to push the ball away but referee Howard Webb [ Images ] thought otherwise, allowing Ronaldo to score from the spot.
Ten minutes later Rooney cut inside and beat the keeper at the near post with a low strike and Spurs suddenly imploded.
Rooney crossed for Ronaldo to head the third and the two swapped roles for the fourth as the England [ Images ] striker's shot rolled in despite Jonathan Woodgate's attempt at a goalline clearance.
Former Spurs player Berbatov rounded it off when he prodded the ball in after Gomes saved his initial header.
"It was a brilliant comeback. We played too slowly in the first half and Tottenham played well," Rooney said.
"The manager told us to quicken our game up and we knew if we scored one we could still win it."
Spurs manager Harry Redknapp [ Images ] said the turning point was the penalty.
"It was a terrible decision. It was a great piece of goalkeeping, he got the ball cleanly," he said.
"There was no danger before that and I thought there were more goals in us. That turned the game. I couldn't see us losing until then. Having said that we conceded some bad goals after."
Earlier, Liverpool had to work hard to beat a Hull team who drew 2-2 at Anfield in December and are now fighting for their Premier League lives.
Hull held their own until first-half stoppage time when Xabi Alonso [ Images ] hit a free kick into the wall before lashing in the rebound.
The home team suffered a further setback when Caleb Folan was sent off for kicking Martin Skrtel [ Images ] and it looked all over as Kuyt headed the second goal in the 63rd minute.
Hull pulled one back with an excellent effort from Geovanni after 73 but, after some nervous moments, the visitors settled it with Kuyt's second.
Chelsea did just about enough at Upton Park, scoring 10 minutes into the second half with Salomon Kalou's [ Images ] first goal in 15 games.
Kalou offered West Ham a way back when he brought down Herita Ilunga in the box, only for Petr Cech [ Images ] to save Mark Noble's 71st-minute penalty.