Manchester City duo Kyle Walker and Kalvin Phillips are included despite fitness concerns.
Manchester United captain Harry Maguire is also included despite being dropped at club level.
Maddison has only one senior cap, back in 2019, and has previously been overlooked by Southgate.
But of the players available to the England boss, only Harry Kane has scored and assisted more Premier League goals in 2022 than the Foxes midfielder.
The absence of Chelsea right-back Reece James means Liverpool’s Trent Alexander-Arnold will go to Qatar despite concerns over his defensive abilities.
Conor Gallagher is another surprise selection in midfield with Southampton’s James Ward-Prowse omitted.
Up front, Callum Wilson was selected ahead of Ivan Toney and Tammy Abraham to be Kane’s deputy.
England begin their World Cup campaign against Iran on November 21 before facing the USA and Wales in Group B.
Squad:
Goalkeepers: Jordan Pickford (Everton), Nick Pope (Newcastle United), Aaron Ramsdale (Arsenal)
Defenders: Trent Alexander-Arnold (Liverpool), Conor Coady (Everton, on loan from Wolverhampton Wanderers), Eric Dier (Tottenham Hotspur), Harry Maguire (Manchester United), Luke Shaw (Manchester United), John Stones (Manchester City), Kieran Trippier (Newcastle United), Kyle Walker (Manchester City), Ben White (Arsenal)
Midfielders: Jude Bellingham (Borussia Dortmund), Conor Gallagher (Chelsea), Jordan Henderson (Liverpool), Mason Mount (Chelsea), Kalvin Phillips (Manchester City), Declan Rice (West Ham United)
Forwards: Phil Foden (Manchester City), Jack Grealish (Manchester City), Harry Kane (Tottenham Hotspur), James Maddison (Leicester City), Marcus Rashford (Manchester United), Bukayo Saka (Arsenal), Raheem Sterling (Chelsea), Callum Wilson (Newcastle United)
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