Didier Drogba sealed the points for Chelsea after Hammers old boy Frank Lampard had set them on their way.
Lampard volleyed Chelsea into the lead after 25 minutes after Yossi Benayoun failed to deal with a throw-in.
But the champions were pegged back when Marlon Harewood followed up his own shot, only seconds after the restart.
Substitute Hernan Crespo rounded Roy Carroll to score 45 seconds after coming on as a substitute and Drogba fired the third with 10 minutes left.
Lampard made his intentions known in the opening minute when testing Carroll with a dipping effort as the predictable boos rang around Upton Park.
But just as the champions were getting into their stride, a reshuffle was caused by an injury to Michael Essien, who, for once, was on the receiving end of a bad tackle from Nigel Reo-Coker.
However, Eidur Gudjohnsen's introduction gave the Blues another attacking option as Arjen Robben moved further infield, freeing up space on the left flank for overlapping full-back Asier del Horno.
Del Horno supplied the ammunition for Robben, who was unlucky with a volley that Carroll managed to keep out, and Drogba, who could have done a lot better.
A Chelsea goal appeared inevitable and that Lampard would be the scorer seemed certain, although he should never have been given the opportunity.
The Hammers defence dithered as they attempted to clear Geremi's long throw.
Benayoun's header was misplaced and could not have fallen kinder for the England midfielder as he silenced the majority of the Upton Park crowd, firing home his 13th Premiership goal of the season.
The Hammers offered little in response before the break, apart from Matthew Etherington seeing his effort cleared off the line by Del Horno.
And even the most optimistic of their followers could have anticipated they would be back on terms within 19 seconds of the restart.
The Chelsea defence was caught square as Harewood latched onto a cute reverse ball from Reo-Coker and was able to follow-up his own shot that bounced following a save by Petr Cech.
Robben missed two good chances to put the champions back in front but a tactical switch from Mourinho proved inspired.
The sight of Drogba being partnered by Hernan Crespo up front is a rare one but the latter netted just 45 seconds after coming on for Damien Duff.
Robben's through ball could have been better timed as he slipped the Argentine striker in on goal, and he rounded Carroll before firing into the roof of the net.
Crespo should have confirmed the victory. He fired wide when sent through again and also shot over from close range seconds later as Chelsea pushed to increase their margin of victory.
But it was left to his strike partner to fire the important third goal, Drogba shooting across Carroll and into the corner of the net after being played through by Gudjohnsen.
West Ham manager Alan Pardew:
"I felt that we gave a good account of ourselves and I thought that the fans were brilliant," said Pardew.
"I cannot fault this team - although we are lacking a bit of quality we stuck at it against a team of superstars.
"We worked hard and made if difficult for Chelsea. In terms of honest endeavour and staying disciplined we did very well."
Chelsea manager Jose Mourinho:
"We have had four matches and four wins in eight days
"That is 12 points and I cannot be happier - the players have been fantastic.
"We made the change, introducing Hernan Crespo, and it worked immediately.
"After that we had many chances to score four of five but West Ham did not deserve that. It was a good game."
West Ham: Carroll, Dailly, Ferdinand, Collins, Konchesky, Benayoun, Fletcher, Reo-Coker, Mullins (Zamora 71), Etherington (Bellion 78), Harewood.
Subs Not Used: Hislop, Clarke, Aliadiere.
Goals: Harewood 46.
Chelsea: Cech, Geremi, Ricardo Carvalho, Terry, Del Horno, Duff (Crespo 60), Essien (Gudjohnsen 13), Lampard, Makelele, Robben, Drogba, Crespo (Wright-Phillips 83).
Subs Not Used: Cudicini, Johnson.
Booked: Duff, Lampard, Gudjohnsen.
Goals: Lampard 25, Crespo 61, Drogba 80.
Ref: H Webb (S Yorkshire).