Cristiano Ronaldo struck two late goals for the rampant Reds after Dimitar Berbatov, Carlos Tevez and Nemanja Vidic had put the champions in control against 10-man West Brom.
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United, who have 50 points from 22 games, also set a new top-flight record of 11 consecutive clean sheets, eclipsing Chelsea's feat in 2004-05. Goalkeeper Edwin van der Sar also surpassed Petr Cech's top-flight streak for not conceding a goal.
Aston Villa climbed into third place on 47 points with England striker Emile Heskey scoring on his debut in a 1-0 victory at Portsmouth.
Tottenham Hotspur eased their relegation fears with a 3-1 home defeat of Stoke City and Sunderland beat Fulham 1-0 thanks to a goal from striker Kenwyne Jones.
Second-placed Liverpool travel to Wigan Athletic on Wednesday when they can move level on points with United.
Liverpool, who set the pace this season but appear to be running out of steam, are now staring up at United who, after a cluster of 1-0 victories, put on a dazzling show of firepower at West Brom.
"The score was important to us and we showed a ruthless streak for the first time this season," United manager Alex Ferguson told Sky Sports.
"Goal difference could play a part and we've always had that over our opponents."
INJURY LIST
West Brom were not helped by having captain Paul Robinson harshly sent off shortly before halftime when they trailed only 1-0 but United, despite a lengthy injury list, were a class apart as they topped up their goal difference.
After the kickoff was delayed by traffic congestion, United took a while to get going and could have fallen behind when the experienced Gary Neville made an uncharacteristic error to allow Jay Simpson an early chance.
Berbatov broke the deadlock with a cool finish past Scott Carson on 22 minutes and after Robinson's dismissal things got worse for the home side when Tevez reacted quickly to score after Carson dropped a cross.
Ryan Donk was unlucky not to pull a goal back for West Brom when his shot struck the woodwork before Vidic headed in a Ryan Giggs corner on the hour to make it 3-0.
Ronaldo then capped a near-perfect night for United with two goals in eight minutes to round off his team's fifth league victory in a row.
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