While clubs will all play each other twice over the course of the season, the ordering of the matches can have a significant impact on their fortunes.
An easy or difficult run at a key stage can create or disrupt momentum, particularly given the additional fixture congestion created by the 2022 World Cup in November and December.
To help unravel this season's fixtures, we analyse the entire 2022-23 Premier League schedule using an aggregation of leading bookmakers' odds and identified the most notable runs.
Manchester City to make fast start
Manchester City will start the new season as favourites to retain their title for a third successive year, especially given their favourable-looking run at the start of the campaign.
Pep Guardiola's side play two of the promoted sides at home in August, and do not face any of the traditional 'big six' until mid-September when they host Tottenham.
Arsenal made a bad start to the season in 2021-22, losing their opening three games by an aggregate of nine goals to nil, but will expect to fare much better this year - a September trip to Old Trafford is the only one of their first eight fixtures against a team expected to finish in the top six.
Palace punished again
Crystal Palace ended last season strongly under Patrick Vieira, taking 10 points from their final six games to finish 12th.
This was after overcoming a difficult start - they played six of the seven toughest teams in their first 10 matches, according to pre-season odds.
Palace can take comfort later in the season with a couple of easier runs - they play the three promoted sides in successive fixtures either side of the World Cup in November and December, before enjoying the same run in the final three games of the campaign.
Chastening start for the Cherries
Bournemouth face a daunting schedule on their return to the Premier League.
After kicking off the season at home to Aston Villa, Scott Parker's men face Man City, Arsenal and Liverpool consecutively.
Nottingham Forest will end their 23-year absence from the top flight with a tricky opening run, playing four of the bookmakers' predicted top eight in August. September will be kinder to Steve Cooper's side as they host their fellow promoted sides at home, either side of a trip to Leeds who narrowly avoided the drop last term.
All three of Forest, Bournemouth and Leeds have been handed tough run-ins, facing two of the 'big six' in their final four games.
Brentford are also likely to need points on the board by mid-April, with Man City, Liverpool, Chelsea and Tottenham among their final six opponents.
Saints' struggles to continue?
Southampton finished last season poorly, taking just one point from their last six matches. Manager Ralph Hasenhuttl could come under early pressure this term as three of Saints' first five games are against teams expected to challenge for a top-four place.
Like Southampton, Wolves also ended last season with a whimper, taking just two points from their final seven games, but unlike the Saints their opening fixtures provide an opportunity to bounce back. Four of their first six league games pit them against opponents who are expected to struggle this season, including two newly-promoted sides.
Newcastle manager Eddie Howe, on the other hand, has some credit in the bank after his side ended 2021-22 in fine form, earning 12 points from their final six games.
The Magpies are tipped by bookmakers to be the leading challengers to the 'big six', but their credentials will be tested with games against Liverpool and Manchester City before the end of August.
Red Devils face scary October
Manchester United will have their squad depth tested to the limit in October as they will have to fit three Europa League group games around a gruelling Premier League schedule.
The Red Devils have six tricky league fixtures during the month, beginning with a Manchester derby at the Etihad and featuring a trip to Chelsea straight after the midweek visit of Tottenham.
The fixture computer has cut Erik ten Hag some slack, however, with the mid-season break for the World Cup bookended by matches against two of the promoted teams and a relatively easy run-in.
With international players likely to have one eye on the World Cup by the time November rolls around, Man City, Liverpool and Spurs have also been handed favourable fixtures either side of the Qatar showpiece.
Thomas Frank's Brentford can once again feel a little hard done by, with games against three of last season's top four scheduled around the World Cup. The Bees' woes are compounded by a trip to West Ham on New Year's Eve two days before hosting Liverpool on January 2.
Later end to the campaign
Due to the World Cup taking place during November and December, the league will have an unprecedented six-week break while the tournament takes place, with a round of fixtures on November 12 and the next one not taking place until Boxing Day.
The upshot of this is that the last round of fixtures will take place on Sunday, May 28, which is far later than usual.
April will be a busy month as a consequence, with six gameweeks planned, while there is little wriggle room for postponed fixtures given the hectic nature of next year.