Frank Lampard took the reins of Chelsea for the first time in a competitive fixture at Old Trafford after taking over from Maurizio Sarri at the start of the summer.
Marcus Rashford fired his side into the lead against the run of play in the first half, firing past Kepa Arrizabalaga from the penalty spot.
Anthony Martial then doubled the advantage 65 minutes in, before Rashford and debutant Daniel James sealed a convincing win for the hosts as Chelsea's resistance crumbled in the last half hour of proceedings.
The result sent United flying up the league table on the opening weekend, with a margin of victory not seen for quite some time.
Not since Sir Matt Busby's brilliant tenure had the Red Devils managed to beat Chelsea 4-0 in a league fixture, a feat which last occurred in March 1965 thanks to a scintillating individual performance from one George Best, then 18, who scored one and set up two more to take down the Blues side managed by Tommy Docherty.
Lampard, meanwhile, had not tasted such a heavy Premier League defeat for the best part of two decades.
United fans might also be cheered to know that Busby's team went on to win the title that season, beating out Leeds United for the First Division crown by virtue of a superior goal average (goals scored divided by games played).
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