The European champions have won seven of their eight league matches to power into a four-point lead, with the manner of their victories just as impressive as the results.
Roberto di Matteo has been keen to play down his side's title chances at this early stage but bringing down second-place United would make that stance untenable.
With Robin van Persie and Wayne Rooney working well in tandem, United has the firepower to worry a Chelsea defence that will be without suspended captain John Terry. But Alex Ferguson's side has been uncharacteristically sloppy at the back this season, conceding first in eight of its 12 matches.
"I can't get to the bottom of it I am afraid," Ferguson said. "If you analyze the goals we are losing, they have come from throw-ins, crosses, cut-backs, all sorts, and they are finding players free in the box.
"It is difficult to put your finger on it, and it is a concern because it is making it difficult for us."
Defending champion Manchester City is level on points with United and can put the pressure on the top two by beating Swansea on Saturday for City to maintain its unbeaten start.
Fourth-place Everton hosts Liverpool in the Merseyside derby on Sunday in the weekend's other big match, while England midfielder Jack Wilshere could make his long-awaited return to Arsenal's first team in the home match against last-place Queens Park Rangers on Saturday.
Tottenham visits Southampton on Sunday as it looks to rebound from a 4-2 home loss to Chelsea last weekend that ended a four-match winning run.
While Chelsea is unbeaten in the league, the team fell to the first loss in its defence of the Champions League title with a 2-1 defeat at Shakhtar Donetsk on Tuesday.
Di Matteo's side was overrun by Shakhtar's Brazilian-led attacking contingent and Chelsea goalkeeper Petr Cech saw the result as a wake-up call.
"In a way, what happened was a good experience for us because we have to defend better," Cech said. "We played well when we had the ball but not when we didn't have it.
"If you do this against Man United, you are in big danger because they are the same type of team. Hopefully it was a good lesson and we learn for the weekend."
Given Chelsea's new-found creativity up front, led at the moment by the imperious Juan Mata, United's shaky defence is sure to come under serious pressure at Stamford Bridge.
With Sunday's match in mind, Rio Ferdinand and Patrice Evra were rested for the 3-2 win over Braga in the Champions League on Tuesday but centre back and captain Nemanja Vidic is still out with a knee injury.
"We have had some great battles with them down the years, but they have changed quite a lot very quickly," United defender Jonny Evans said of Chelsea. "You can see that from the way they have been scoring their goals this season.
"They scored four again at the weekend so it's going to be a tough game and our record down there has not been great over the last few seasons, so that makes it a bit harder still."
Terry will be absent as he serves the second match of his four-game domestic ban for racially abusing QPR defender Anton Ferdinand in a league game last October.
The repercussions of that on-field incident have been vast, including a worsening in relations between Rio Ferdinand, Anton's older brother, and Chelsea defender Ashley Cole, who gave evidence on behalf of Terry in a criminal court.
In the latest handshake saga in the Premier League, Ferdinand is widely expected to snub Cole in the pre-match protocol. United is set to be without Shinji Kagawa, who has a knee injury, while Frank Lampard could be missing for Chelsea because of a calf problem.
Also on Sunday, it's: Newcastle vs. West Bromwich Albion.
Saturday's other matches are Aston Villa vs. Norwich, Reading vs. Fulham, Stoke vs. Sunderland and Wigan vs. West Ham.