The Old Trafford faithful will bid an emotional farewell to Sir Alex Ferguson as he takes charge of his final home game in the Premier League, while there are key games in the battle for survival and the race for a top-four finish.
Wigan Athletic may be in FA Cup final action against Manchester City on Saturday but they are sure to have a keen eye of the fortunes of their fellow strugglers as they could be pushed closer to relegation if results go against them.
Stoke City have a difficult match against Champions League-chasing Tottenham Hotspur, while Norwich City host West Bromwich Albion, Newcastle United travel to Queens Park Rangers and Sunderland lock horns with Southampton.
Elsewhere, Fulham face Liverpool and Everton take on West Ham United in their first fixture since it emerged this week that David Moyes would be leaving to replace Ferguson at Manchester United.
The news that Ferguson will be retiring at the end of the season has dominated the headlines over the past few days and it is sure to be a special occasion on Sunday as Manchester United welcome Swansea City to Old Trafford. The Red Devils have already clinched the title, their 13th league crown in 26-and-a-half glorious years under Ferguson, but there will be an extra determination to put on a good show against a Swansea side heading for a top-half finish.
Sunday's early kick-off, live on Sky Sports 1HD, pits Stoke against Tottenham. Tony Pulis' Potters can breathe easier now that a three-match unbeaten run has lifted them on to 41 points and a secure mid-table standing, but they will be looking to finish the season with a flourish and derail Spurs' pursuit of a top-four spot. Andre Villas-Boas' men are currently fifth and, trailing Arsenal by a point, they are no longer in control of their own destiny, although they can put the pressure on their North London rivals by winning at the Britannia Stadium.
Everton's chances of a top-four finish have finally been extinguished and the focus will soon turn to finding a successor to Moyes, who will bring an 11-year reign at Goodison Park to an end when he officially joins Manchester United at the start of July. He is certain to get a warm send-off in his final home game as Everton boss against West Ham, and the Toffees will be desperate to stay above Merseyside rivals Liverpool and clinch Europa League qualification. The Hammers, meanwhile, will be aiming to hold on to a place in the top 10 in their first season back in the Premier League.
There are a number of crucial matches at the bottom, where QPR and Reading have already been consigned to relegation and Wigan are three points adrift of safety. Newcastle are the team directly above the drop zone and will have been relieved to see the Latics lose to Swansea in midweek, but they still have work to do to secure survival and will have identified Sunday's encounter at QPR as one they must win. The Magpies bounced back from being demolished by Liverpool to draw with West Ham last time out, but QPR also battled hard in a 1-0 loss to Arsenal and will not want to end the season in last place.
Norwich are level on points with Newcastle and also looking nervously over their shoulders, but one more victory should ensure they beat the drop. With a trip to Manchester City to follow on the final day of the season, the Canaries will hope to ease their anxiety by triumphing at home to West Brom. Chris Hughton's men have lost to Stoke and Villa in their two most recent matches but the Baggies have also suffered back-to-back defeats against Wigan and Man City.
Sunderland and Southampton are both still in trouble despite looking at different times as though they had killed off any lingering relegation fears. Saints have been sucked back into the scrap for survival after a four-match winless run and still need a victory to be absolutely safe, while Sunderland's goal difference means they too should stay up with just one more win.
The final game of the weekend sees Fulham host Liverpool at Craven Cottage in a game between two teams in very different form. Fulham are still not mathematically safe after losing four games in a row since hitting the 40-point mark, while Liverpool are unbeaten in six and could still overtake Everton despite being held to a goalless draw in last week's Merseyside derby.