Raheem Sterling’s double and goals from Aymeric Laporte, Rodri and Phil Foden moved Pep 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 do lose one of their remaining games against Wolves, West Ham and Aston Villa.
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.
Liverpool remain in contention for a historic quadruple of trophies, but their 1-1 draw at home to Tottenham on Saturday opened the door for City to extend their lead at the top of the table.
City showed no signs of physical fatigue or a mental hangover from Madrid as they took full advantage.
Guardiola freshened his side up with four changes to the side that started in the Bernabeu.
Kyle Walker was ruled out by the recurrence of an ankle injury, while Bernardo Silva, Phil Foden and Riyad Mahrez were left on the bench.
But City’s strength in depth shone as Sterling, Jack Grealish, Ilkay Gundogan and Oleksandr Zinchenko all starred in a brilliant team performance.
A comfortable afternoon for the home side could have been very different had Chris Wood not headed straight at Ederson early on, with the unmarked Joelinton also waiting at the back post to apply the finishing touch.
Chances also came and went at the other end in a frantic opening as Laporte blasted over from a corner and Joao Cancelo failed to turn in Kevin De Bruyne’s teasing cross.
Cancelo made amends by creating the opener as he headed across goal for Sterling to nod in his first Premier League goal since February.
Newcastle had the ball in the net moments later when Wood turned in from a corner, but the offside flag had already been raised against Bruno Guimaraes.
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 atoned for his earlier miss by smashing 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.
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