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Juan Mata, making his 200th Premier League appearance, gave United the lead after just three minutes, with Fellaini’s goals followed by a late tap in for Romelu Lukaku, who scored for the 11th time in 10 games.
Watched from the stand by their former midfielder David Beckham, Jose Mourinho’s side kept the pressure on title rivals Manchester City, who were due to play at Chelsea in Saturday’s late game.
Palace, meanwhile, remain without a point or a goal in the league this season, and rarely looked like ending either sequence against opponents who have now scored 31 times in a 10-match unbeaten run in all competitions.
Mourinho made five changes to a team that had only arrived home from Russia in the early hours of Thursday morning following their midweek Champions League victory over CSKA Moscow.
There was little sign of early sluggishness, though, as they scored in the third minute from their first attack thanks to two players left out of the starting line-up on Wednesday.
Marcus Rashford showed clever footwork to deceive Palace full-back Joel Ward down the left, then pulled the ball back for the unmarked Mata to sweep in from 12 yards.
That was a huge setback for a Palace team who had been beaten on each of their previous 10 league visits to Old Trafford, since a 2-1 victory in December 1989.
They had lost striker Christian Benteke before the game with a knee injury that is expected to keep him out for six weeks, but despite going behind so early, they started to cause more of a threat.
Centre-back Mamadou Sakho headed over from a free-kick played in from the right by Yohan Cabaye after Ashley Young had brought down Ward near the corner flag, and United had to defend a series of corners after that.
– Pressure –
Bakary Sako, the winger pushed into service as a striker to replace Benteke, almost equalised as he ran in from the left on to Andros Townsend’s diagonal through ball, but goalkeeper David De Gea beat away the drive at his near post.
United, though, rode out the pressure and added a second goal 10 minutes before half-time, with Young crossing from the left for Fellaini to volley in from close range at the far post.
Chris Smalling almost added a third, heading just wide from Henrikh Mkhitaryan’s corner, before Rashford’s shot was blocked at the near post by goalkeeper Wayne Hennessey.
United’s third goal arrived in the fourth minute of the second half, shortly after Rashford had been denied by a Ward block.
Rashford was involved in the goal and looked initially as if he might try to claim it as his free-kick, whipped in from the left, flew in at the far post.
But television replays showed beyond doubt that Fellaini had flicked the ball with his forehead inside the six-yard box, and the Belgium midfielder claimed his second of the match.
The match lost most of its momentum after that, with Sako volleying over a half-chance for Palace, before Lukaku steered wide at the other end when he looked certain to score.
As United sought a fourth, Hennessey advanced from his line and spread himself to block Anthony Martial as the substitute ran into the penalty area on to Mkhitaryan’s pass.
The fourth goal arrived in the final minutes, with Martial attacking down the left and crossing low for Lukaku to score from close in.
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