No side has ever won four consecutive English top-flight titles, but City are closing in on that feat after a 5-1 victory over Luton moved them two points clear of their title rivals with six games to play.
Aston Villa's 2-0 win at Arsenal also had major ramifications in the battle for Champions League football next season as they move three points clear of Tottenham, who were thrashed 4-0 at Newcastle.
AFP Sports looks at three talking points from the Premier League weekend.
Fortress Anfield crumbles
Liverpool had not tasted defeat in any competition at Anfield for 14 months but are now licking their wounds after two in four days left their season at risk of fizzling out.
Captain Virgil van Dijk said Atalanta's 3-0 win in the Europa League on Thursday "hurt" but Crystal Palace's 1-0 victory may sting even more given the context of a finely balanced title race.
A week ago the destiny of the title was in Liverpool's hands, but they have now won just three times in eight games in all competitions as a weary squad limps towards the finish line.
Jurgen Klopp's men defied expectations during an injury crisis in the first few months of 2024 to win the League Cup and remain in contention for three other trophies.
But the quest for the quadruple is long gone and what was set to be a fitting farewell for Klopp is rapidly unravelling.
Emery exacts revenge on Arsenal
Unai Emery made his first return to a full Emirates since he was sacked as Arsenal boss in 2019 and may end up prolonging the Gunners' 20-year wait to win the title.
Emery's Villa have done the double over Mikel Arteta's men this season and produced a mature away performance the Spaniard was rightly proud of.
The visitors had to ride their luck during an Arsenal onslaught in the first half but took control in the second before striking late through Leon Bailey and Ollie Watkins.
A four-time Europa League winner, Emery also has Villa on course for their first trophy in 28 years as they lead Lille 2-1 after the first leg of their Europa Conference League quarter-final.
And the 1982 European Champions are on the verge of a return to Europe's top table for the first time since the competition was rebranded the Champions League.
Isak invaluable to Newcastle project
Alexander Isak is closing in on Erling Haaland in the race for the Golden Boot after the Swedish striker scored twice against Tottenham.
With 17 goals in 24 Premier League games this season, Isak is beginning to deliver on the potential that lured Newcastle into paying Real Sociedad £63 million ($78 million) for his signature less than two years ago.
Injuries have at times hindered his progress at St. James' Park, but at 24 he is now blossoming into a world-class talent.
Newcastle chief executive Darren Eales has admitted the Magpies may have to sell a prime asset to invest further into the squad due to pressures of meeting the Premier League's financial sustainability rules.
But Eddie Howe is adamant that cannot mean letting Isak go even as the likes of Arsenal and Manchester United are rumoured to hold an interest.
"We're trying to build a team," said Howe.
"We're trying to grow everything upwards and to do that as quickly as possible and efficiently as you can you need to keep your best players."
