Manchester primed for final denouement
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 Manchester clubs all season with United top until the beginning of October, before City went ahead until the start of March. United then opened up an eight-point lead by Easter time.
That evaporated after an erratic run and City went back to the summit on goal difference on April 30 when they beat United 1-0 at the Etihad Stadium.
The race for third place and the automatic spot in next season's Champions League is just as close as the battle for the title but involves three teams.
Arsenal are favourites to take it as they are currently third with 67 points, followed by Spurs on 66 and Newcastle on 65.
Arsenal are at West Bromwich Albion, playing their last game under new England manager Roy Hodgson, Spurs face a Fulham side at White Hart Lane coached by their still-popular former manager Martin Jol and Newcastle travel to in-form Everton.
All three will want to avoid finishing fourth, which normally carries with it a guaranteed place in the Champions League qualifiers but not this season.
Chelsea, who will finish sixth, their lowest position since 2002, will take the fourth Champions League spot if they beat Bayern Munich in the Champions League final on May 19, making third place an even greater prize for the chasing trio.
Spurs help third spot for four months before a dip in form coincided with manager Harry Redknapp being linked to the England job, but they appear to have regained their momentum with just two league defeats in their last nine.
Arsenal have only taken two points out of a possible 12 and Newcastle have come up fast on the rails, despite their defeat by City.
Bolton also have it all to do at Stoke City where even a win will not save them if QPR get a draw in Manchester.