Their superiority will be hammered home if they win at home to Norwich, and local rivals and reigning champions Manchester United fail to pick up any points on their trip to Aston Villa.
With 11 wins and two draws from their opening 13 league matches, City — who beat Arsenal in the quarter-finals of the League Cup midweek — have hardly put a foot wrong in domestic action all season.
But City have so far endured a faltering Champions League campaign, which could mean they fail to qualify for the knockout stages of the rich competition.
Sheikh Mansour, the Abu Dhabi-based businessman who has invested around £1bn into the north-west club, said domestic success was his priority this season.
“We must not forget that our main objective is to win the English Premier League and if we achieve that, then it will have an impact on the team and the club as a whole and will show we can achieve anything,” Mansour told the Al Ittihad newspaper.
United will try to recover from having their second-string side knocked out of the League Cup by Championship club Crystal Palace when they travel to Villa Park.
Sir Alex Ferguson came as close as he ever does to criticising his players by insisting their midweek display was “not a Manchester United performance” and someone who will be especially keen to make a mark on Saturday is defender Ashley Young, a £16m pre-season capture from Villa.
Under-pressure Chelsea manager Andre Villas-Boas takes the misfiring Blues to fourth-placed Newcastle insisting he won’t abandon the brand of football that helped him guide Porto to a trophy treble last season.
Also facing an unwelcome spotlight is Chelsea and England captain John Terry, with prosecutors considering whether to press charges against the defender over allegations he racially abused QPR’s Anton Ferdinand in a recent west London derby.
Third-placed Tottenham, seven points behind City heading into the weekend, will look to continue their impressive start to the season at home to Bolton.
Meanwhile, bottom of the table Blackburn are at home to Swansea while QPR take on West Brom and Arsenal travel to Wigan.
On Sunday, Sunderland, in their first match since sacking manager Steve Bruce, travel to fellow strugglers Wolves, with Everton facing Stoke.
Liverpool, now without injured Brazil midfielder Lucas Leiva for the rest of the season, are away to Fulham on Monday.