Edin Dzeko grabbed two and Yaya Toure also got on the scoresheet as City all but booked a trip to Wembley by piling on the misery for the Hammers and their under-fire manager Sam Allardyce.
City needed just 12 minutes to take the lead at the Etihad Stadium and the Londoners were simply swept aside in an embarrassingly one-sided match.
Allardyce, who was taunted by visiting fans late in the game, had prioritised the game to some extent by fielding a weakened side against Nottingham Forest in the FA Cup third round last weekend.
But that backfired as they were thrashed by six goals and despite eight changes, including the return of senior players such as Mark Noble, Joe Cole, Guy Demel and Mohamed Diame, it proved a similar story in the Manchester rain.
It was also a particularly chastening debut for Roger Johnson, who looked well off the pace after arriving on loan from Wolves to bolster the defence this week.
With cup football now effectively over, this weekend's trip to Cardiff in the Barclays Premier League is taking on crucial importance for Allardyce.
For City, it was another irresistible display to add to a growing catalogue that has already seen them put six past Arsenal and Tottenham and score seven against Norwich this season.
They might even have had more but for a number of good saves from Hammers goalkeeper Adrian.
Summer signing Negredo's treble took his tally for the season to 18, one behind injured team-mate Sergio Aguero. BBC Sports
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