The Londoners came to Old Trafford to prove a point and came away with three after a master-class second-half performance.
The result also broke two Premiership records for most points (94) and most wins (29).
United had set out to put a dent in Chelsea's golden season and the Red Devils more than held their own in an even first half.
They even took the lead in the seventh minute when Ruud van Nistelrooy scored his first league goal since the end of November and his first in open play in the Premiership at Old Trafford this season.
Chelsea failed to clear a Wayne Rooney corner and Roy Keane, on the far side of the box, fed the ball to Paul Scholes 25 yards out.
Scholes' shot was only cleared to Rooney on the left and his low and hard cross was turned home by Van Nistelrooy four yards out.
But United's lead lasted only ten minutes. Claude Makelele found Tiago free and in space 30 yards from goal and he scored with a superb right-foot shot which sailed into the top corner of the net past static United goalkeeper Roy Carroll.
United's hopes were raised early in the second half when Darren Fletcher's blistering 25-yard drive crashed against the Chelsea bar. But Chelsea were now beginning to weave their passing magic.
Glen Johnson had made a hash of one easy chance when played through by Joe Cole, but Eidur Gudjohnsen made no such mistake in the 61st minute.
Tiago's glorious throughball ripped open the United defence for the Icelander to race clear and chip his shot over Carroll and into the net from 12 yards.
Chelsea made it 3-1 eight minutes from time.
Wes Brown's dreadful cross-field pass found Chelsea's Frank Lampard on the left and his ball to the near post was turned home by Cole, although he appeared to be offside.