The Cottagers' celebrations at the final whistle will surely have been matched at Anfield. Victory for Liverpool against Aston Villa on Sunday will see United's lead cut to just one point, albeit with a game in hand.
Sir Alex Ferguson, who at least saw Chelsea beaten by Spurs on an incredible day in the Premier League, will need all his managerial experience to galvanise his troops ahead of the visit of Aston Villa on 5 April.
United's frustration at Craven Cottage was epitomised by Cristiano Ronaldo, who twice had to be warned by referee Phil Dowd for his petulant complaining and was booked for a reckless lunge at Murphy in the second half.
In truth, Ronaldo, like his team-mates, was completely out of sorts, harried into giving the ball away with shocking regularity in a first half in which Fulham were rampant.
Fortune and team effort delight Hodgson
Roy Hodgson's side, who had leaked seven goals without response in their two previous games against United this season, peppered Van der Sar's goal with 10 shots before half-time, while limiting the opposition to just two.
Quicker in the tackle and always willing to test Van der Sar from distance, they fully deserved their lead when it came.
Former Fulham keeper Van der Sar did well to keep out Zamora's header from a corner, but the rebound came straight back to the striker and as he nodded towards goal, Scholes instinctively put his arms up.
Scholes knew what was coming as he stayed on his knees, looking ruefully at the ground.
As the midfielder trudged down the tunnel, Murphy confidently stroked the penalty high into the net.
It continued an incredible scoring record for Murphy, who three times gave Liverpool a 1-0 win against United in his Anfield days.
Fulham continued to take the game to United, with Zamora in particular terrorising the visitors' creaking defence.
They should have had a second when Andrew Johnson miscontrolled and then Clint Dempsey blazed over from a good position.
And it looked as if Fulham would pay for failing to make the most of their dominance as United came out fighting after the break.
Dimitar Berbatov, who landed awkwardly on his ankle at the end of the first half, was replaced by Rooney at half-time and the change gave United some much-needed urgency.
Phelan plays down defeat by Fulham
Darren Fletcher shot too close to Schwarzer after a one-two with Ronaldo, who could also only find the keeper with a free header from Rooney's cross.
United fans were on their feet when Ronaldo set up Ji-Sung Park in front of goal but Schwarzer not only kept his effort out but was up quickly to keep out Rooney's follow-up.
And Fulham wrapped up victory through Gera, who had his back to goal when he collected Johnson's cross but managed to flick the ball up and hook it home.
The sight of the second goal going in proved too much to bear for Rooney, who threw the ball away when a free-kick was taken from the wrong place to pick up his second booking.
The England striker gave Dowd a volley of abuse before storming down the tunnel, punching the corner flag for good measure on the way.
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