Michael Owen set United on their way five minutes after the break, with teenager Federico Macheda adding two more.
But it was a barren night for Dimitar Berbatov who, despite assurances about his future from manager Sir Alex Ferguson, could have most to lose from a big-money transfer for Wesley Sneijder.
With speculation mounting over an imminent deal for the Inter Milan playmaker, both Nani and Berbatov have something to prove.
Nani was only a substitute in the Champions League final defeat to Barcelona in May and Berbatov did not even make it that far, spending the evening on his own in tearful contemplation about his Wembley fate.
To that end, the Bulgarian could have done with tucking away the first decent chance of the game, five minutes before half-time, when Fabio charged to the byline and cut a perfect cross back for the striker.
With only the goalkeeper to beat, Berbatov should have found the net.
Instead, his side-footed effort was pushed away by Matt Reis.
As Berbatov was amongst a trio of players who made way at the break, it was not a satisfactory conclusion to the evening.
Wayne Rooney was also substituted at the interval after failing to tuck home Nani’s far-post cross, although he has nothing to prove after finding his form at the back end of United’s record 19th Premier League title-winning campaign.
Should Sneijder’s arrival from Inter eventually be completed, it would offer Ferguson an additional attacking option and a replacement for the retired Paul Scholes.
What leaves Berbatov more vulnerable is that Owen has a future given the 31-year-old has signed a one-year contract extension, when most observers anticipated him being amongst those released in the summer.
The clinical manner in which he put United ahead in front of a record 51,000 friendly crowd at the Gillette Stadium emphasised why he was selected on the bench ahead of Berbatov for the defeat to Barcelona.
Owen may not have the pace of old but he retains accuracy in his shooting boots and a neat finish from a tight angle compared favourably with Berbatov’s failure.
Macheda added a second five minutes later, although the hosts responded almost immediately as they capitalised on being awarded a dubious free-kick when Benny Feilhaber’s shot deflected in off Kenny Mansally.
Another neat finish from Macheda – zero goals in 14 appearances on loan with Sampdoria last season – soon followed.
After a tortuous summer in his personal life, Ryan Giggs received a warm reception upon his arrival and it was his pass that provided United with a fourth, for Park Ji-sung.