City coach Pep Guardiola threw on Jack Grealish and Riyad Mahrez - both guaranteed starters for many other teams - in the 60th minute, replacing England winger Phil Foden and Portugal's Bernardo Silva.
Within three minutes, Grealish sent in a pinpoint cross for Mahrez to win the match for City.
The victory at Stamford Bridge, against an injury-hit and out-of-form Chelsea, moved City to within five points of Arsenal who failed to pierce Newcastle United's defence on Tuesday in a 0-0 draw at the Emirates Stadium.
While Arsenal have put their faith in the relatively inexperienced Eddie Nketiah as the man to replace injured striker Gabriel Jesus, City can count on Argentine World Cup winner Julian Alvarez should they need a back-up for goal machine Erling Haaland.
Despite the array of top-name stars at his disposal, Guardiola heaped most praise on 18-year-old Rico Lewis who came off the bench at halftime to replace wing back Joao Cancelo and helped turn the game in City's favour.
"This young boy has the ability and quality to not just play good, but to make his mates better. This is so difficult to find," the Spaniard said. "Right now, he is fundamental for us."
Chelsea coach Graham Potter, whose early unbeaten run in charge of the Blues seems a distant memory after picking up only six of the last 24 points available, was left to rue the injuries that have added to his challenge at Stamford Bridge.
England midfielder Mason Mount was a surprise omission from the squad after picking up a training-ground knock and within the first 22 minutes, Raheem Sterling and Christian Pulisic were withdrawn due to injuries.
Also unavailable on Thursday were a string of players including wing back Reece James, defender Wesley Fofana and midfield anchor N'Golo Kante.
"I've never experienced anything like it," Potter said. "We want ... a fully-fit squad and to be able to compete... It's frustrating for everybody at the moment."
He said Mount might be available to face Manchester City on Sunday in the FA Cup and hoped Pulisic's injury was not too serious.
GREALISH'S STRUGGLES
Grealish said adapting to the team's style of play has been much more difficult than he imagined, almost 18 months after his league record 100 million pounds transfer from Aston Villa.
The 27-year-old bagged his third Premier League assist of the campaign and matched his tally from last season, but he still had more league goals and assists in his final season at Villa than he has had since his August 2021 move to City.
"When I came here, I'll be honest, it was so much more difficult than I thought," Grealish told Sky Sports after City's 1-0 win.
Grealish registered six goals and 10 assists for Villa in the league in 2020-21 but only has four goals and six assists in the competition since joining City.
"In my head I thought I was going to the team sitting top of the league and I was going to get so many goals and assists and obviously it isn't the case. A lot of teams tend to sit in against us and that wasn't the case at Villa," Grealish said.
"(Former Villa manager) Dean Smith would tell me to go and find the weak link in the defence, whether that was on the right, the middle or whether I wanted to hug the touchline - and at Villa, I always had an overlapping full-back.
"I came into City, having been at Villa my whole life, and I've never had to change. I've always been used to that. I didn't realise how hard it is to adapt to a different team and manager."
Manchester City host Chelsea in the FA Cup on Sunday.
