Liverpool moved up to second in the table as Chelsea suffered a shock defeat and Manchester City were held.
• Brewin: United slump into crisis
Liverpool saw off West Ham United 4-1 to overtake Chelsea, who lost to Stoke for the first time in the Premier League era, and City, who had to settle for a draw at Southampton.
Manchester United, meanwhile, suffered yet more misery as they lost at home to Newcastle while, at the foot of the table, Crystal Palace continued their revival under Tony Pulis with victory over Cardiff City and Norwich City claimed a confidence-boosting win at West Bromwich Albion.
Oussama Assaidi scored a superb injury-time goal to hand Stoke City a 3-2 victory over Chelsea.
With the clock ticking over the 90-minute mark, Assaidi, on loan from Liverpool, cut in from the left-hand side and hammered an unstoppable shot into the top corner.
Chelsea had taken an early lead when Andre Schuerrle rifled the ball into the bottom-right corner from outside the box after just nine minutes. However, Jose Mourinho's side were made to pay for missing several chances with Peter Crouch scoring from close range after Petr Cech failed to claim the ball from a corner three minutes from the break.
Stoke piled on the pressure straight from half-time and it paid dividends when Stephen Ireland curled in a delicious effort before Assaidi gave Stoke their first league victory over Chelsea since 1975.
Liverpool ran out comfortable winners in the end against West Ham but will be sweating on the fitness of their captain Steven Gerrard after a 4-1 win at Anfield.
Four own goals were scored in the game, with Guy Demel putting through his own net in the first half, while James Collins also bundled into his goal under pressure from Martin Skrtel to put Liverpool 2-0 up.
The Reds looked to be in cruise control, but Gerrard left the field with what appeared to be a hamstring strain midway through the second half, and West Ham seized the initiative, pulling a goal back through Skrtel's own goal -- his second in seven days.
After Madibo Maiga missed a sitter from four yards, Liverpool made the game safe through Luis Suarez's strike in the 81st minute, and Kevin Nolan was then sent off for a heavy challenge on Jordan Henderson. Joey O'Brien was then credited with another own goal from a Suarez effort.
Southampton ended a run of three straight defeats by coming from a goal down to draw 1-1 with Manchester City. Southampton came into the game on the back of losses to Arsenal, Chelsea and Aston Villa, and they were under pressure just 10 minutes into the clash with City as Aguero put the visitors in front with a neat first-time finish to grab his 18th goal of the season.
However, Manuel Pellegrini's men were hit when Dani Osvaldo produced a fine equaliser to curl the ball beyond Costel Pantilimon three minutes before half-time after wriggling past Vincent Kompany.
Newcastle United recorded their first victory at Old Trafford in 41 years and inflicted a second 1-0 home defeat in four days on Manchester United as David Moyes' predicament went from bad to worse.
The home side were denied a penalty when Vurnon Anita handled the ball on the line in the second half, and minutes later Newcastle capitalised with a sweeping counter-attack that Yohan Cabaye finished with a low strike into the bottom left corner.
United had the ball in the net soon after as Robin van Persie headed home, but the flag was raised for offside and the hosts were unable to restore parity.
Newcastle’s victory ends a wait of 15,471 days for Newcastle United to win at Old Trafford, and leaves United with an uphill battle if they are to finish in the top four.
Goalkeeper Hugo Lloris' error saw Adam Johnson score an opener for Sunderland, but Spurs hit back as Paulinho levelled and an own goal in the second half made it 2-1 to take all three points.
John O'Shea inadvertently turned Moussa Dembele's 50th-minute cross past keeper Vito Mannone to hand the visitors the points and leave the Black Cats deep in trouble at the foot of the table. It was the fifth time this season a Black Cats player had put through his own goal, more than any man in red and white has achieved at the other end.
Defeat was all the more galling as the home side, just as they did against Chelsea in midweek, took the lead when Johnson capitalised on Lloris' blunder to score his first league goal of the season. But Paulinho levelled within six minutes and Spurs never looked back, and had their finishing been better - Jermain Defoe twice hit the post and fired wide when through on goal - they would have won far more comfortably.
Crystal Palace continued their bid for safety with their second consecutive win since Tony Pulis took over at Selhurst Park with a 2-0 win over fellow strugglers Cardiff.
Palace took an early lead, with Cameron Jerome heading in Jason Puncheon's cross from six yards to score against his former club after six minutes, and the points were wrapped up when Marouane Chamakh scored a superb goal midway through the second half.
The former Arsenal striker, who notched the winner against West Ham in Pulis' first game in charge on Tuesday, controlled the ball on his chest after from Barry Bannan's cross and smashed a volley into the bottom corner.
Two other troubled sides went head-to-head at The Hawthorns where West Brom took on Norwich, and it was the visitors who took the three points with a 2-0 victory.
The Canaries went ahead against the run of play on 13 minutes with Gary Hooper smashing a low shot home from Leroy Fer's defence-splitting pass, and it was Fer who made the points safe with just two minutes left on the clock when he wrong footed Boaz Myhill after a good first touch.