Raheem Sterling’s double and goals from Aymeric Laporte, Rodri and Phil Foden moved Guardiola’s men three points clear of Liverpool with three games left to play.
City also edged four goals ahead of the Reds on goal difference, which could still decide the title if the defending champions lose one of their remaining games against Wolves, West Ham and Aston Villa.
“If some people doubted us they don’t know this team,” said Guardiola. “It’s one of the best groups I ever trained in my life.”
“It was a perfect afternoon. Before the start of the game I felt our crowd were disappointed but not upset and angry about who we are as a team and what we have done the last five years.”
The title is the only trophy left for City to fight for after blowing the chance to reach a second consecutive Champions League final, against Real Madrid on Wednesday.
The Spanish giants came from two goals down in the dying stages to win a classic semi-final 6-5 on aggregate and set up a meeting with Liverpool in Paris.
Guardiola was quick to point out that what happened in Madrid is a lesson that there is still a long way to go in the final three games.
But this has the potential to be the decisive weekend in the title race after Liverpool were held 1-1 at home by Tottenham on Saturday.
City showed no signs of physical fatigue or a mental hangover as they took full advantage, but they do have injury problems for the run-in.
Kyle Walker and John Stones were absent from the starting line-up and captain Ruben Dias was forced off at half-time.
Guardiola confirmed all three are out for the season with Nathan Ake also nursing an ankle problem.
“Everything can happen, if it happened in 56 seconds (against Madrid), it can happen in three games. So calm and prepare for Wolves on Wednesday.”
Guardiola freshened his side up with four changes to the side that started in the Bernabeu with Bernardo Silva, Foden and Riyad Mahrez were left on the bench.
City’s strength in depth shone through as Sterling, Jack Grealish, Ilkay Gundogan and Oleksandr Zinchenko all starred in a brilliant team performance.
Sterling has been a peripheral figure in recent months, but scored his first league goals since February at a vital time.
The England international opened the scoring by nodding home Joao Cancelo’s header across the box.
City’s strength from set-pieces has played a huge role in putting them in pole position to retain the title.
Guardiola’s men scored twice from dead balls at Leeds last weekend and did so again to put the game beyond the Magpies.
Laporte smashed home from close range seven minutes before the break after Dubravka spilled Gundogan’s drive from a well-worked De Bruyne corner.
De Bruyne was the creator again for the third as his corner was headed in at the near post by Rodri.
Only a Dubravka wonder save denied Zinchenko a fourth with a powerful rising drive.
The City fans were able to bask in cries of “championees” for the final quarter and two more goals in stoppage time gave them the insurance of a goal difference cushion even if they are to drop points in the next fortnight.
Foden came off the bench to steer home Zinchenko’s low cross before he and Grealish combined to tee up Sterling for his second of the game.