Last season's Premier League runner-up began its assault on the title in fine fashion against a Yohan Cabaye-less Newcastle side that had Steven Taylor sent off in the first half.
First-half goals from David Silva and Sergio Aguero gave City an early lead, before Magpies center back Steven Taylor was given a straight red card for hitting out at the diminutive Argentine goalscorer just before the break.
The home side's dominance continued in the second period, with Yaya Toure marking his 100th Premier League appearance by curling a free kick past Tim Krul just after the restart. Substitute Samir Nasri completed the scoring with 15 minutes remaining.
Fernandinho, who arrived from Shakhtar Donetsk in the offseason, was handed a competitive City debut along with Spain international Jesus Navas. But Alvaro Negredo, who joined with Navas from Sevilla, was only named among the substitutes.
Newcastle was without loan signing Loic Remy due to a calf injury, but perhaps of more interest to the St James' Park faithful was the omission of Arsenal target Yohan Cabaye, with manager Alan Pardew confirming the club had received a bid in the build-up to the game for the 27-year-old midfielder.
City started the game with plenty of intent and the early pressure led to the breakthrough in just the sixth minute.
Silva played in Edin Dzeko to the left-hand side of the penalty area, and his low cross was deflected straight into the path of the Spaniard, who continued his run into the box and headed past the wrong-footed Krul.
Newcastle thought it had found a quick response when Hatem Ben Arfa jinked his way to the edge of the area before playing a sublime through-ball to Yoan Gouffran who fired beyond the reach of Joe Hart. Gouffran's celebrations, though, were curtailed by the offside flag.
City then had a huge shout for a penalty when Dzeko's perfectly weighted pass was collected by Toure deep in the box. He appeared to be tripped by Mathieu Debuchy, but referee Andre Marriner waved away the protests.
In the 22nd minute, City did deservedly double its lead. Vincent Kompany supplied Dzeko and he showed great vision to play a nonchalant back-heel straight into Aguero's path. The Argentina international drove at Taylor onto his favored right foot before firing expertly across Krul into the far corner.
Aguero then had a legitimate claim for a penalty when Taylor appeared to handle his strike in the box, but Marriner was unmoved. It was only a brief reprise for the Newcastle defender, though, whose evening was brought to a premature end moments later when he was shown a straight red card for striking the back of Aguero's head with his arm.
City picked up where it left off in the second half, and Dzeko was again thwarted by Krul, who produced a superb athletic save to keep out the Bosnian's point-blank header.
But the third arrived in the 50th minute. Aguero won a free kick left of center of the goal, and Toure curled his effort into the top corner and past the despairing dive of Krul.
The one sour note for City came with 20 minutes remaining when captain Kompany was replaced by Javi Garcia after the center back had injured himself sliding for a challenge on Sammy Ameobi.
But it did not impact on City's fluency in attack, and Nasri made it four when he pounced on a loose ball in the 75th minute before coolly slotting beyond Krul.
Negredo came on to replace Silva with 10 minutes remaining and had the ball in the net only to be ruled offside, but it made no difference as City secured three comfortable points.