Eidur Gudjohnsen's early goal gave Jose Mourinho a winning start at Chelsea.
Gudjohnsen took advantage of a weak challenge by Manchester United goalkeeper Tim Howard to scramble home the winner after 14 minutes.
It was harsh on Sir Alex Ferguson's depleted side, who enjoyed the majority of possession but could not cash in.
Summer signing Alan Smith headed wide from a good chance and Ryan Giggs missed a similar opportunity with 10 minutes left as Chelsea hung on.
United's injury problems saw captain Roy Keane forced into central defence, while Chelsea gave a debut to Russia captain Alexei Smertin after a year on loan at Portsmouth.
Ferguson's ravaged side created the first opportunity when Giggs' dangerous cross found Smith, but he headed a good opportunity off target.
Chelsea took advantage of the reprieve to take the lead after 14 minutes, catching United on the break in lethal fashion.
Quinton Fortune was beaten to a clearance by Geremi, whose cross was knocked into Gudjohnsen's path by Didier Drogba.
The Icelandic striker evaded a desperately feeble challenge from United goalkeeper Howard to bundle home the opener.
United were enjoying plenty of possession, but were blunted without the threat of injured strikers Ruud van Nistelrooy and Louis Saha.
And when a chance did fall to Paul Scholes after 31 minutes, he screwed uncharacteristically off target.
Frank Lampard had been a subdued figure, but he almost doubled Chelsea's lead before the interval when he fired a free-kick inches wide.
United continued to carry the fight to Chelsea after the break, with Mourinho's side being held comfortably at arm's length.
And Mourinho made a change with 20 minutes left, replacing £24m striker Drogba, who had been quiet, with another new boy Mateja Kezman.
Ferguson attempted to provide a cutting edge himself by replacing the disappointing Eric Djemba-Djemba with Diego Forlan, but he failed to make an impact.
Giggs then missed United's best opportunity with 10 minutes remaining, heading wide from eight yards after he was picked out by Smith's cross.
Chelsea: Cech, Paulo Ferreira, Gallas, Terry, Bridge, Geremi, Makelele, Lampard, Smertin, Drogba, Gudjohnsen. Subs: Cudicini, Mutu, Kezman, Parker, Ricardo Carvalho.
Man Utd: Howard, Silvestre, Gary Neville, Keane, Fortune, Miller, O'Shea, Djemba-Djemba, Giggs, Scholes, Smith. Subs: Ricardo, Phil Neville, Bellion, Richardson, Forlan.
Referee: G Poll (Hertfordshire)