At the same time, Arsenal, Tottenham Hotspur or Newcastle United will seal a Champions League place and Queens Park Rangers or Bolton Wanderers will join relegated Blackburn Rovers and Wolverhampton Wanderers in the Championship next season.
None of those seven clubs can afford a slip-up on an afternoon that will bring down the curtain on a season which has taken one unlikely twist after another.
With just 90 minutes plus stoppage time left to play Manchester City know that if they beat Queens Park Rangers at the Etihad Stadium, they will be champions for the first time since 1968 unless United defeat Sunderland by at least nine goals more than City win by.
Both teams have 86 points while City have an eight-goal better goal difference than their neighbours. City have scored 90 goals, United 88 and even in this goal-crazy season such a huge winning margin is highly unlikely.
However, if City should draw or lose to QPR, United would retain their title and be crowned champions for the 20th time with a win at Sunderland.
An added twist is that QPR's manager is Mark Hughes, who a former United player who was sacked as City manager in 2009 to make way for Roberto Mancini.
For weeks Mancini has said United remained favourites to take the title, but he changed tack slightly after City's 2-0 win at Newcastle last weekend.
"It is not finished. It is important that we get three points and we need a big effort - there is one game more," he said.
"QPR will be tough, they are fighting to avoid relegation. Nothing changes. It is ours to lose. It doesn't depend on other teams any more."
United manager Sir Alex Ferguson said City would find it tough against Rangers.
"The whole future of the club could be resting on the game and I only wish Sparky [Hughes] was playing," he said after United beat Swansea City last weekend.
"Mark knows his job all right. He was sacked by City in a very unethical way and he'll remember that. Mark Hughes' teams always fight but QPR players are fighting for survival."
Hughes said: "It would be a fantastic story if we were able to go there and get something, they are going for titles and we are trying to stay in this league."
Hughes hopes of keeping QPR up were boosted by Djibril Cisse's 89th-minute winner against Stoke City last weekend and Cisse, who has either scored or been sent off in all seven matches he has played for the club, believes QPR can survive.
"I've always said we're going to stay up - I believe in the club and the players," the French striker said.
"We have a great manager and we're trying to build something really strong around the club.
First place in the title race has fluctuated between the Manches
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