West Ham United will begin the restructured Barclays Premier Reserve League South season with the visit of Manchester City on Tuesday 7 September.
With a number of clubs choosing not to take part in the competition in 2009/10, the league has been reorganised, with teams taking on every other side at least once during the campaign.
As such, the Hammers will face Arsenal, Aston Villa Chelsea, West Bromwich Albion and Wolverhampton Wanderers home and away, while facing the ten Barclays Premier Reserve League North clubs once.
Meanwhile, the club has also taken the decision to change both the regular venue and kick-off times for home fixtures, with matches now taking place during the afternoon at the Academy training ground at Little Heath, unless otherwise stated.
The changes also mean the likes of Manchester City, Wigan Athletic, Bolton Wanderers, Newcastle United and Manchester United will visit the south east, while Alex Dyer's squad will travel north to take on Everton, Liverpool, Blackpool, Sunderland and Blackburn Rovers.
Dyer said the new league structure was exciting for both himself and his players.
"It's great for the players to go to places up north when usually they would just be coming up against teams from down south. It will open up their eyes a little bit because they will be going to training grounds and football stadiums they have never been to before.
"They will also be playing against players that they don't know too much about and others who they will have only previously seen on television.
"I want them to go to these places and give a good account of themselves, not only because we want to do West Ham United proud, but also because these are the experiences that will stand them in good stead when they are members of the first-team squad in the future."
Before the league season gets under way, the reserves will contest friendly matches at League Two side Burton Albion on Saturday 24 July and Blue Square South outfit Bishop's Stortford on Thursday 29 July.
Barclays Premier Reserve League South 2010/11 fixtures
Tue 7 Manchester City (H) 2pm
Tue 14 Everton (A) 2pm (at Finch Farm Training Ground)
Tue 28 Wigan Athletic (H) 2pm
Tue 5 Liverpool (A) 7pm (at Tranmere Rovers FC)
Tue 12 Bolton Wanderers (H) 2pm
Tue 19 Arsenal (A) 1pm (at London Colney)
Wed 27 Blackpool (A) 3pm (at Bloomfield Road)
Mon 15 Aston Villa (A) 12pm (at Bodymoor Heath Training Ground)
Tue 23 Chelsea (H) 1pm
Tue 30 West Bromwich Albion (H) 1pm
Tue 7 Wolverhampton Wanderers (A) 7pm (at AFC Telford United)
Tue 11 West Bromwich Albion (A) 7pm (at The Hawthorns)
Tue 25 Aston Villa (H) 1pm
Wed 16 Chelsea (A) 2pm (at Cobham Training Ground)
Tue 22 Wolverhampton Wanderers (H) 2pm
Tue 1 Arsenal (H) 2pm
Tue 8 Sunderland (A) 3pm (at Eppleton Colliery Welfare Ground)
Tue 15 Newcastle United (H) 2pm
Mon 28 Blackburn Rovers (A) 2pm (at Blackburn Rovers FC Training Ground)
Tue 5 Manchester United (H) 2pm
Home games to be played at West Ham United FC Academy Training Ground, Little Heath Sports Ground, Hainault Road, Romford, Essex, RM6 5SS, unless otherwise stated.