Tottenham will host champions Man City on a mouthwatering opening weekend of the new Premier League season, while Thomas Tuchel faces a nightmare start to his first full campaign in charge of Chelsea, with trips to three 'Big Six' rivals in the first five matches.
On a huge first round of fixtures in mid-August, City's trip to north London is the stand-out game - and the match could even see Harry Kane face Spurs in his first game for City should his rumoured summer move come to fruition.
Elsewhere on the opening weekend, Manchester United host Leeds, Liverpool travel to newly-promoted Norwich and Chelsea host a London derby against Crystal Palace.
Thomas Tuchel faces a nightmare start to his first full Premier League season at Chelsea
Leeds travel to Old Trafford to face Manchester United on the opening weekend of 2021-22
2021-22 OPENING WEEKEND FIXTURES
Brentford v Arsenal
Burnley v Brighton
Chelsea v Crystal Palace
Everton v Southampton
Leicester City v Wolverhampton
Manchester United v Leeds United
Newcastle United v West Ham United
Norwich City v Liverpool
Tottenham Hotspur v Manchester City
Watford v Aston Villa
But it's not their opening game Tuchel will be most concerned about, with visits to Arsenal, Liverpool and Tottenham coming in the first five matches of the season, before the Blues host champions City in their sixth game.
It is a far easier start for Manchester United, meanwhile, with Leeds, Southampton, Wolves, Newcastle, West Ham, Aston Villa and Everton ahead of the first international break of the season.
In fact, Ole Gunnar Solskjaer's side don't face a top-six rival until October 16 when they travel to Leicester, before hosting Liverpool the following weekend.
On the final day of the season, Chelsea, Leicester, Liverpool and Manchester City will all enjoy home advantage, facing Watford, Southampton, Wolves and Aston Villa respectively.
Fans of the three promoted teams - Norwich, Watford and Brentford - will of course be desperate to find out who they play on the opening weekend of their return to the Premier League, and it is a huge welcome back for the Championship champions.
The Canaries welcome Jurgen Klopp's Liverpool to Carrow Road, looking to secure a first victory over the Merseyside giants since April 1994.
City travel to Tottenham on the opening day - and could it be Harry Kane against his old club?
Ole Gunnar Solskjaer will be delighted, with United not facing a top-six rival until October 16
Watford, meanwhile, host Aston Villa and Brentford have two immediate London derbies to look forward to with Arsenal at home and Palace away their first two.
Bees fans will also be keeping a keen eye on their fixture dates against Chelsea, with the two west London derbies coming on October 16 at Brentford, and April 2 at Stamford Bridge.
On the subject of derbies, the first Manchester clash of the season comes at Old Trafford on November 6, while the reverse fixture at City comes on March 5.
In north London, Spurs and Arsenal fans will be anticipating their rivalry once more, with September 25 and January 15 the two dates to look out for, the former at the Emirates and the latter at Tottenham.
In fact, January 15 - the 22nd matchday of the season - is set to be one of the most exciting, with the north London derby also joined by Manchester City vs Chelsea, and Palace also travel to their rivals Brighton on the south coast.
German friends Daniel Farke and Jurgen Klopp will reunite for Norwich-Liverpool in the opener
Wolves have a tough Christmas run, with Chelsea, Arsenal and United all in quick succession
Boxing Day regularly throws up some eye-catching fixtures and this year is no different, with big-six rivals Manchester City and Leicester facing off at the Etihad, while Liverpool host Leeds and Manchester United are away at Newcastle.
Just two days later, Leicester's tough Christmas run continues as they host Liverpool, with Chelsea-Brighton and Brentford-Man City the other picks.
On New Year's Day there is a mouthwatering set of fixtures as Arsenal host Manchester City and Liverpool travel to Chelsea, while Manchester United host Wolves to complete a nightmare few days for the Midlands side.
New boss Bruno Lage will not be overly excited for their tough Christmas fixtures, which see them face Chelsea, Watford, Arsenal and Manchester United in the space of 14 days.