United will have Jadon Sancho available for selection, but Raphael Varane's transfer has not been completed in time to feature on the opening day against Leeds.
Here, we look back at some classic encounters between two of the game’s traditional big rivals.
Man Utd edge thriller
Current Manchester United boss Ole Gunnar Solskjaer scored twice but Sir Alex Ferguson’s side lived on their nerves as they clung on for a 4-3 win in the Premier League in March 2002.
Paul Scholes saw his early opener cancelled out by Leeds’ Mark Viduka but the visitors powered ahead with Solskjaer’s brace and a Ryan Giggs effort.
An Ian Harte free-kick gave Leeds hope before Lee Bowyer set up a rousing finish by turning in a miscued Robbie Fowler shot.
Harte almost snatched an equaliser from another set-piece but his curling effort narrowly missed the target.
Joy for Leeds during top-flight exile
Leeds endured a long and often difficult absence from the Premier League between 2004 and 2020 but there were occasional bright spots for their fans, such as their surprise FA Cup third-round win at Old Trafford in 2010.
Jermaine Beckford scored the only goal as then League One Leeds stunned Ferguson’s United, 42 league places above them, 1-0.
It was the first time Ferguson had suffered defeat in the third round or been beaten by a lower-division side in the competition.
The goalless draw played out between the sides in March 1993 was far from a classic in terms of the action, but the wider picture surrounding Eric Cantona’s return to Elland Road ensured that particular Premier League game would live long in the memory.
The Frenchman had controversially quit the Yorkshire club for Old Trafford months earlier in what was arguably the most significant transfer of Ferguson’s 26-year reign.
The Leeds fans made their feelings known in what was a raucous, tense atmosphere. Cantona responded in unpleasant fashion and was later fined £1,000 for spitting at Leeds supporters.
Butt clinches dramatic win
Nicky Butt grabbed the winner as United, early in their treble-winning season, dug deep to see off Leeds 3-2 at Old Trafford in November 1998.
Jimmy Floyd Hasselbaink gave Leeds the lead with a low shot that rattled in off the post before two quickfire goals either side of half-time from Solskjaer and Roy Keane put United ahead.
Leeds, who were forced to replace injured goalkeeper Nigel Martyn with a 19-year-old Paul Robinson, hit back through Harry Kewell but Butt settled it with a fine strike.
Local boys win it for Leeds
It was not until September 1994 that Leeds claimed their first win over United of the Premier League era, and when it came it was two local stars who made the difference.
David Wetherall and Brian Deane were the men on target as Leeds claimed a memorable 2-1 victory at Elland Road.
Cantona pulled one back from the penalty spot, much to home fans’ frustration, but Leeds were not to be denied.