The Hammers won the 2015/16 competition, then known as the Under-21 Premier League Cup, after beating Hull City on penalties at the KCOM Stadium.
They meet Leicester, Brighton & Hove Albion and Nottingham Forest in Group E, in a competition that pits Premier League 2 sides against Category Two and Three clubs who contest lower-tier leagues.
The top two teams in the eight groups reach the last 16, and that round along with the quarter-finals, semi-finals and final will all be one-off knockout ties. They go to extra-time and penalties if the teams cannot be separated.
Like Premier League 2, clubs are allowed to field players under the age of 23, or born before 1 January 1993. Each team can select three over-age outfield players and an overage goalkeeper.
Dates and venues for matches within the group stages will follow in due course.
Southampton, Newcastle United, Swansea City, Bristol City
Sunderland, Cardiff City, Blackburn Rovers, Burnley or Watford*
Manchester City, Colchester United, Derby County, Hull City
Everton, Norwich City, Wolverhampton Wanderers, Portsmouth or Barnsley*
Leicester City, Brighton & Hove Albion, West Ham United, Nottingham Forest
Middlesbrough, Charlton Athletic, Fulham, AFC Wimbledon
Liverpool, Huddersfield Town, West Bromwich Albion, Ipswich Town
Reading, Sheffield United, Stoke City, Birmingham City
*Burnley host Watford and Portsmouth face Barnsley in the Premier League Cup Qualifying Round on 12 September