The competition is contested by 64 teams during the initial group stage, with every club from League One and Two taking part along with 16 invited Premier League under-21 sides.
The teams will be divided into 16 regional groups consisting of four clubs who play each other once. One under-21 team will compete in each group.
In the event of a draw after 90 minutes, a penalty shoot-out will be held, with the winning team earning an additional point.
The top two from each group will progress to the knockout stages, the first two rounds of which remain regionalised by north and south before an open draw from the quarter-finals onwards.
The Papa John’s Trophy Round One draw will take place live on Sky Sports at 4:30pm on Thursday.
Other Premier League under-21 teams taking part include Arsenal, Aston Villa, Brighton & Hove Albion, Chelsea, Crystal Palace, Everton, Leicester City, Manchester United, Newcastle United, Southampton, Tottenham Hotspur, West Ham United and Wolves.
The Carabao Cup Round One draw will also take place live on Sky Sports at 3:40pm on Thursday, while the League One fixture list for the 2021/22 season will be released at 9am on the same day.
Wednesday were knocked out of the EFL Cup in the Third Round last year by Premier League opponents, Fulham, and haven’t played in the EFL Trophy since the 2011/12 season.