Second-half strikes from the recalled Mario Balotelli, his first league goal of the season, and James Milner gave second-placed Manchester City a 2-0 victory at Wigan Athletic.
The Manchester clubs, on 33 and 32 points respectively, have opened up a notable gap on their title rivals after 14 games, with Chelsea seven points off the pace in third.
Boos rang out again at Stamford Bridge where new Chelsea interim manager Rafael Benitez, brought in last week to replace the axed Roberto Di Matteo, was left waiting for his first goal and win after a second successive 0-0 draw - Fulham securing a point in the West London derby.
The jeers and abuse that greeted Benitez in his first game in charge on Sunday were notably less vocal but the Spaniard did little to win over the doubters.
"I am a little frustrated. The team is well organised and created chances against a team that works hard, so you can see us going forward, but still we have to improve," Benitez told reporters.
Chelsea, on a run of six games without a league win, still leapfrogged West Bromwich Albion into third place on goal difference after Albion's impressive start to the campaign was checked by a 3-1 defeat at Swansea City.
Tottenham Hotspur moved up to fifth by beating Liverpool 2-1 at White Hart Lane, rising above Everton and Arsenal who drew 1-1 at Goodison Park.
Dutch striker Van Persie needed little time to make his mark at Old Trafford, his ninth league goal of the season coming inside a minute when his shot deflected off James Collins and over the head of helpless goalkeeper Jussi Jaaskelainen.
United have never lost a Premier League game at Old Trafford in which they have led at the break and although they failed to add to their advantage, West Ham huffed and puffed with no end product.
Unbeaten City kept tabs on their rivals with a workmanlike display at the DW Stadium - securing a sixth successive win over Wigan.
Balotelli, who has found opportunities limited under Roberto Mancini this season, drifted in and out of the game until he broke the deadlock on 69 minutes.
GOAL DROUGHT
James Milner rifled in a second from outside the box three minutes later but Mancini thought his side were lucky to win.
"It was important because it's always a difficult game because they play very well and [Roberto] Martinez is a great manager. We were lucky. I think I am lucky," he said.
At Stamford Bridge, Benitez kept faith with underperforming Fernando Torres but the striker's league goal drought has now extended beyond 10 hours.
The Spaniard was denied in the second half by goalline clearance from Aaron Hughes but Fulham had their moments - John Arne Riise wasting one glorious opportunity and also forcing Petr Cech into a fine save.
Chelsea fans again showed their dissatisfaction at the popular Di Matteo's sacking - chanting his name throughout the 16th minute - his former squad number.
Wayne Routledge scored twice for Swansea as they brushed aside West Brom, while Gareth Bale had an eventful night for Spurs.
The Welshman's strong run and cross allowed Aaron Lennon to net on seven minutes and Bale soon doubled the lead with a free-kick that deflected off the wall and past a wrongfooted Liverpool keeper Pepe Reina.
Bale gifted Liverpool a lifeline 18 minutes from time - not that he knew much about it as Lennon's goal-line hack smacked him in the face and flew in for a painful own goal.
Arsenal, who appeared jaded in a goalless draw
