Arsenal face an immediate test of their title credentials against a revamped Manchester United, while a new-look Liverpool launch the new Premier League season at home to Bournemouth Friday.
Newcastle United are set to be without wantaway star striker Alexander Isak for a tough trip to Aston Villa.
Let’s look at the key talking points ahead of the first weekend of the 2025/2026 season.
Debut delight for Sesko or Gyokeres?
Benjamin Sesko and Viktor Gyokeres are set to make their Premier League debuts for United and Arsenal respectively at Old Trafford after a summer that could have seen them line up for the opposition Sunday.
Arsenal were linked with a move to Sesko for over a year before deciding to bet on Gyokeres as the man to fire them to a first Premier League title since 2004 for a fee that could rise to £66m ($89m).
The Gunners have finished second for the past three seasons and were lacking a clinical finisher to take that final step towards being champions.
Gyokeres netted a remarkable 97 times in 102 games during two years at Sporting Lisbon, much of which came under the orders of United boss Ruben Amorim.
Instead of being reunited with the Swede, Amorim has been given the resources to overhaul his attack with the signings of Sesko, Bryan Mbeumo and Matheus Cunha at a combined cost of over £200m.
United endured their worst season since being relegated in 1974 during Amorim's first year in charge.
The Red Devils finished 15th in the Premier League and failed to qualify for Europe after losing the Europa League final.
Both clubs desperately need a fast start and the battle between the two new No 9s will go a long way to deciding the outcome.
Liverpool ready despite revamp
Liverpool have bucked the trend by outspending their rivals with a squad overhaul fresh from winning the league.
Only once, Manchester City in 2019, have the Premier League champions been the biggest spending English club in the market since 2007.
A £260m outlay on Florian Wirtz, Hugo Ekitike, Jeremie Frimpong and Milos Kerkez is far from over with Isak and Crystal Palace captain Marc Guehi linked with moves to Anfield.
Trent Alexander-Arnold, Luis Diaz and Darwin Nunez are among those to have been sold to raise funds, while the club are still reeling from the tragic death of Diogo Jota in a car accident last month.
The transition has exposed some teething problems in pre-season as a slick attacking force has been picked off on the counter-attack.
Arne Slot, though, is confident his side are ready as they look to defend the title for the first time since 1984.
"I think we’ve lost five to six players that played quite a lot of minutes for us last season and we brought in four new ones, so then it’s normal that there’s a little bit of adaptation," said Slot.
"But we are definitely ready for the league to start."
Can Villa, Newcastle rattle big six again?
As the Premier League's traditional "big six" of Liverpool, City, United, Arsenal, Chelsea and Tottenham Hotspur have flexed their financial muscle in the transfer market, Villa and Newcastle have been squeezed out.
Constrained by the need to meet financial sustainability rules, Villa's only major signing has been Ivorian stiker Evann Guessand from Nice.
Newcastle boss Eddie Howe has had to field constant questioning on the status of Isak, who sat out pre-season preparations in a bid to force through a desired move to Liverpool.
The Magpies attempts to replace the Swede have repeatedly fallen down with Sesko, Mbuemo, Ekitike, Liam Delap and Joao Pedro among those to opt for moves elsewhere.
But both Villa and Newcastle have consistently outperformed some of the "big six" in recent seasons and will be targeting Champions League qualification again this season.
Fixtures (Bangladesh time)
Friday
Liverpool v Bournemouth, 1am Saturday
Saturday
Villa v Newcastle, 5:30pm
Brighton v Fulham, 8pm
Sunderland v West Ham, 8pm
Tottenham v Burnley, 8pm
Wolves v Man City, 10:30pm
Sunday
Chelsea v Palace, 7pm
Forest v Brentford, 7pm
Man Utd v Arsenal, 9:30pm
Monday
Leeds v Everton, 1am Tuesday