Liverpool's frustrating draw with Tottenham Hotspur on Saturday offered City the opportunity to go three points clear at the summit with just three games to play, and Pep Guardiola's side made no mistake with a scintillating performance at the Etihad Stadium.
Raheem Sterling's opener settled any lingering nerves following Wednesday's semifinal collapse against Real Madrid, which had seen City -- seemingly cruising through to a second straight final -- concede twice at the death before Karim Benzema completed the fightback in extra-time.
Goals from Spanish duo Aymeric Laporte and Rodri against Newcastle were followed by late strikes from Phil Foden and Sterling, adding further gloss on a near-perfect weekend for City, who will retain its Premier League crown with victories over Wolves, West Ham and Aston Villa regardless of Liverpool's efforts.
Despite the continued elusiveness of the Champions League, another league victory would mark a fourth in five years for the Citizens, and simultaneously end Liverpool's pursuit of an unprecedented quadruple.
After a tumultuous week, it was a "perfect afternoon" for Guardiola, whose faith in his team responding to midweek's defeat was never shaken.
"With what this team have done, do you have any doubt?" Guardiola told Sky Sports.
"We are five years doing this every three days. If some people doubted us they don't know this team.
"It's one of the best groups I ever trained in my life," he added.
An entertaining opening saw both sides squander excellent chances before Sterling nodded home Joao Cancelo's cushioned header.
His 83rd league goal under Guardiola, the 27-year-old has now surpassed Sergio Agüero as the club's highest league goalscorer during the Spanish coach's tenure.
Many a beautiful goal have been scored at the Etihad since Guardiola's arrival in 2016 -- City's second was not one of them.
Newcastle goalkeeper Martin Dubravka fumbled Ilkay Gundogan's bouncing strike into the path of Ruben Dias, his subsequent save presenting the ball to Laporte, who bundled home for his fourth league goal of the season.
City fans might have been forgiven for not being content with a two-goal advantage after the Madrid collapse, but as the home side's possession count ticked closer to 70%, even the most pessimistic must have relaxed after Rodri added the third.
The Spaniard escaped his marker to head home De Bruyne's corner for his third league goal in as many games. For a team renowned for its flowing passing moves, incredibly, it marked City's Premier League-high 20th set-piece goal of the season, according to BBC Sport.
Callum Wilson's squandered one-on-one miss compounded a disappointing day for the visitors, but Newcastle's season has long been safe after initial fears of relegation.
Spurred by the Saudi-Arabian backed consortium takeover in October, a January spending spree helped rocket the Tyneside club up the table, with a top-half finish still possible.
Goals in the games closing moments from Sterling and Foden meant that City fans could -- this time -- enjoy two late goals in a game.
"We showed the personality we have after the defeat we have that is incredible [against Madrid]," Rodri told Sky Sports.
"But football is like this, we have to wake up because you have to stay focused on the Premier League ... still we are in the fight. The personality we showed today was unbelievable."
Arsenal edge closer to Champions League return
Elsewhere, an early brace from Eddie Nketiah secured a crucial 2-1 win for Arsenal over Leeds United in its chase for a Champions League spot, heightening Leeds' fears of relegation.
Despite playing with 10 men for over an hour after Luke Ayling's first half red card, Diego Llorente's header set up a nervy finish for fourth-placed Arsenal, who head into Thursday's hotly-anticipated derby against Spurs with a four-point advantage over their North London rivals.
Defeat for Leeds saw the Yorkshire club fall into the relegation zone, its misery compounded by Everton's 2-1 victory at Leicester which lifted it out of the bottom three.
West Ham joined Manchester City in bouncing back from midweek European disappointment, routing already-relegated Norwich 4-0 to ease the pain of Thursday's Europa League semifinal defeat to Eintracht Frankfurt.