City are seven points clear of fourth-placed Liverpool, with a game in hand, and could kill off any hopes of a revival for Jurgen Klopp’s men with a first victory at Anfield for 18 years.
At the other end of the table, Sheffield United, West Brom and Fulham have been cut adrift and look destined for a return to the Championship.
But struggles for Liverpool, Chelsea, Tottenham and Arsenal have opened up the race for a Champions League place, with a host of other contenders aiming for a top-four finish.
Man City leave Liverpool trailing
Despite the vast sums invested and multiple trophies won since Shiekh Mansour’s takeover 13 years ago, Anfield has remained an unassailable fortress for the men in blue with City’s last victory there coming in 2003.
However, Liverpool’s invincibility at home has crumbled in recent weeks in front of empty stands.
After a club-record 68-game unbeaten run in the Premier League at Anfield, the Reds have suffered back-to-back 1-0 defeats to Burnley and Brighton.
Liverpool have not won any of their past four home games - and have not found the net there since late December.
Klopp admitted his side were suffering from mental and physical fatigue as an injury crisis in defence continues to have an impact on the rest of the team, with midfielders Fabinho and Jordan Henderson forced into deputising at centre-back.
Goalkeeper Alisson Becker, Fabinho and Sadio Mane all missed the Brighton defeat on Wednesday but could return for the daunting task of halting City’s 13-game winning run in all competitions.
Despite the absence of Kevin De Bruyne, City have found the kind of form that enabled them to pip Liverpool to the title by a single point in the 2018/19 season.
Pep Guardiola’s men have conceded just one goal in winning their past nine league games to storm three points clear at the top with a game in hand over second-placed Manchester United.
“At the end the aim is to be champion,” said Guardiola, looking ahead after easing past Burnley on Wednesday. “It is the same (three) points, but against a contender.”
Champions League dreams
Liverpool remain fourth for now despite their faltering form but just nine points separate them from Arsenal in 10th spot.
Sixth-placed Everton are six points behind Leicester, in third spot, but have two games in hand.
However, tomorrow, Carlo Ancelotti’s men travel to face a Manchester United side fresh from equalling the Premier League’s record winning margin, with a 9-0 demolition of nine-man Southampton.
West Ham can move above Liverpool when they visit Fulham, while Tottenham and Chelsea will be confident of bolstering their push for a top-four finish when they face struggling West Brom and Sheffield United respectively.
Arsenal desperately need to win at Aston Villa to keep their chances of a return to the Champions League next season alive.
Bottom three doomed?
A bad week for Fulham and West Brom combined with recent wins for Burnley, Brighton, Newcastle, Wolves and Crystal Palace has opened up an eight-point gap between the bottom three and survival.
“It leaves us with a great gap to fill,” said West Brom boss Sam Allardyce after taking just one point from games against Fulham and Sheffield United.
The Blades are the only side in the relegation zone showing signs of life, with three wins in their past five games, but Chris Wilder’s men have given themselves a mountain to climb after picking up just two points from their opening 17 games.
All of the bottom three face tough fixtures this weekend, but failure to win could see the relegation dogfight peter out with a whimper.
Fixtures (all Phuket times)
Aston Villa v Arsenal (7:30pm)
Burnley v Brighton (10pm)
Newcastle v Southampton (10pm)
Fulham v West Ham (12:30am)
Manchester United v Everton (3am)
Tottenham v West Brom (7pm)
Wolves v Leicester (9pm)
Liverpool v Man City (11:30pm)
Sheffield United v Chelsea (2:15am)
Leeds v Crystal Palace (3am)