West Ham had seen a second-string team embarrassed 5-0 at Nottingham Forest in the FA Cup on Sunday, but even the return of several first-team players could not prevent a mauling by City's ruthless forwards in the semi-final first leg.
A smartly taken brace from Negredo and a goal from the marauding Yaya Toure put City 3-0 up, with Negredo completing his hat-trick in the second half before Edin Dzeko sealed victory with two goals of his own.
<img src="http://images.mid-day.com/images/images/2014/jan/negredo.jpg" alt="Alvaro Negredo, Silva" /> Alvaro Negredo celebrates with David Silva. Pic/ AFP
Manuel Pellegrini's City have now scored 59 goals in their 15 home games to date this season and their place in the final appears a formality ahead of the return leg at Upton Park on January 21.
"It's never finished until the end, but I think that today we have one leg in the final," City manager Pellegrini told Sky Sports.
"For me the most important thing was not to score the six goals, but it was the way that this team must play. It's very important to continue scoring goals, but also it's very important not to concede goals.
"We have to play another game, the second leg, in London and we'll try to continue to play, independent of what we did here today."
For injury-ravaged West Ham, meanwhile, focus will reluctantly return to the fight to haul themselves out of the Premier League relegation zone.
"It's not unique to us, is it? Manchester City have done this to Tottenham and Manchester United," said manager Sam Allardyce.
"We knew they had to have an off night and they didn't. Their finishing was outstanding in every sense of the word.
"We haven't got a fully fit squad and we are in a hole and we need to dig ourselves out."
Allardyce made eight changes to the team thrashed at Forest, handing a debut to new loan signing Roger Johnson, while Toure and Vincent Kompany were among the returning players in a strong City XI.
Speaking ahead of the game, which took place a day after Manchester United lost 2-1 at Sunderland in the other semi-final, Allardyce said that a draw would be an ideal result, but the visitors were quickly overrun.
Samir Nasri had driven a low cross across the face of goal and Javi Garcia had headed wide from a David Silva corner by the time Negredo broke the deadlock in the 12th minute.
It was a goal of arresting simplicity, with Negredo haring onto a raking 60-yard pass from Toure and lashing an impeccable left-foot volley into the bottom-right corner.
After West Ham goalkeeper Adrian saved from first Silva and then Nasri, Negredo made it 2-0 in the 26th minute with a shot into the roof of the net from strike partner Dzeko's through ball.
Toure had given City a scare by limping to the touchline after injuring himself in a slide tackle, but after returning to the fray he added to the hosts' lead with a characteristic driving run followed by a low shot.
Had Dzeko shown more composure, City's half-time lead might have been even greater, but at no point did West Ham threaten to turn the game into a contest.
Allardyce introduced Carlton Cole up front at half-time, but within four minutes City were four goals up as Negredo completed his hat-trick by sweeping home a shot from Silva's deflected pass.
It was the Spaniard's second City hat-trick, after a treble against CSKA Moscow in November, and Dzeko got in on the act in the 60th minute when he converted a low cross from Gael Clichy.
As West Ham's fans took to angrily goading Allardyce, City took their foot off the pedal, but in the 89th minute Aleksandar Kolarov got to the byline and cut the ball back for Dzeko to complete the rout.

Alvaro Negredo plundered a hat-trick as Manchester City destroyed hapless West Ham United 6-0 at the Etihad Stadium on Wednesday to all but qualify for the League Cup final

Negredo's hat-trick helps Man City beat West Ham 6-0

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Negredo's hat-trick helps Man City beat West Ham 6-0

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