Wayne Rooney's killer instinct gave United the lead when he superbly turned in a cross from Brazilian full-back Rafael da Silva at the near post after 28 minutes.
Midfielder Michael Carrick doubled the lead four minutes later with a low shot after a cut-back from Antonio Valencia.
Rafael added the third on the stroke of halftime with a left-footed shot after making a smart turn on the edge of the area and Dimitar Berbatov put the result beyond doubt on 50 minutes with a close-range effort.
Lively winger Valencia completed the rout in the 75th minute with a delightful finish.
United are second in the league table with 43 points, two adrift of Chelsea who defeated Fulham 2-1 on Monday.
Arsenal, third on 41 points but have a game in hand, crushed bottom side Portsmouth 4-1 at Fratton Park.
Goals from Eduardo, Samir Nasri, Aaron Ramsey and Alexandre Song handed them a third consecutive victory.